WorldWideScience

Sample records for animal toxicity study

  1. STUDY OF THE TOXIC EFFECTS OF CYPERMETHRIN IN EXPERIMENTAL ANIMALS

    Directory of Open Access Journals (Sweden)

    Syed Mehmood Hasan

    2016-06-01

    Full Text Available This study focuses on the toxic effects of a commercially available pesticide, cypermethrin (CM, on animals. This pesticide was administered in the form of aerosol spray through a nebulizer. The study was performed in four different groups and a constant dose of the pesticide was administered once, twice, thrice and four times a day to the respective group for a period of 30 days. The animals were then dissected to study the pesticide effects on different organs. The organs were preserved in 10% formalin. The tissues were processed by basic histopathological method and the slides were prepared for observation. The results were recorded on a performa and were quantified by a unique scoring system. It is concluded that the injurious effects to the mentioned organs were dose and frequency dependent.

  2. Are quantum dots toxic? Exploring the discrepancy between cell culture and animal studies.

    Science.gov (United States)

    Tsoi, Kim M; Dai, Qin; Alman, Benjamin A; Chan, Warren C W

    2013-03-19

    Despite significant interest in developing quantum dots (QDs) for biomedical applications, many researchers are convinced that QDs will never be used for treating patients because of their potential toxicity. The perception that QDs are toxic is rooted in two assumptions. Cadmium-containing QDs can kill cells in culture. Many researchers then assume that because QDs are toxic to cells, they must be toxic to humans. In addition, many researchers classify QDs as a homogeneous group of materials. Therefore, if CdSe QDs are harmful, they extrapolate this result to all QDs. Though unsubstantiated, these assumptions continue to drive QD research. When dosing is physiologically appropriate, QD toxicity has not been demonstrated in animal models. In addition, QDs are not uniform: each design is a unique combination of physicochemical properties that influence biological activity and toxicity. In this Account, we summarize key findings from in vitro and in vivo studies, explore the causes of the discrepancy in QD toxicological data, and provide our view of the future direction of the field. In vitro and in vivo QD studies have advanced our knowledge of cellular transport kinetics, mechanisms of QD toxicity, and biodistribution following animal injection. Cell culture experiments have shown that QDs undergo design-dependent intracellular localization and they can cause cytotoxicity by releasing free cadmium into solution and by generating free radical species. In animal experiments, QDs preferentially enter the liver and spleen following intravascular injection, undergo minimal excretion if larger than 6 nm, and appear to be safe to the animal. In vitro and in vivo studies show an apparent discrepancy with regard to toxicity. Dosing provides one explanation for these findings. Under culture conditions, a cell experiences a constant QD dose, but the in vivo QD concentration can vary, and the organ-specific dose may not be high enough to induce detectable toxicity. Because QDs

  3. Developmental and reproductive toxicity of inorganic arsenic: animal studies and human concerns.

    Science.gov (United States)

    Golub, M S; Macintosh, M S; Baumrind, N

    1998-01-01

    Information on the reproductive and developmental toxicity of inorganic arsenic is available primarily from studies in animals using arsenite and arsenate salts and arsenic trioxide. Inorganic arsenic has been extensively studied as a teratogen in animals. Data from animal studies demonstrate that arsenic can produce developmental toxicity, including malformation, death, and growth retardation, in four species (hamsters, mice, rats, rabbits). A characteristic pattern of malformations is produced, and the developmental toxicity effects are dependent on dose, route, and the day of gestation when exposure occurs. Studies with gavage and diet administration indicate that death and growth retardation are produced by oral arsenic exposure. Arsenic is readily transferred to the fetus and produces developmental toxicity in embryo culture. Animal studies have not identified an effect of arsenic on fertility in males or females. When females were dosed chronically for periods that included pregnancy, the primary effect of arsenic on reproduction was a dose-dependent increase in conceptus mortality and in postnatal growth retardation. Human data are limited to a few studies of populations exposed to arsenic from drinking water or from working at or living near smelters. Associations with spontaneous abortion and stillbirth have been reported in more than one of these studies, but interpretation of these studies is complicated because study populations were exposed to multiple chemicals. Thus, animal studies suggest that environmental arsenic exposures are primarily a risk to the developing fetus. In order to understand the implications for humans, attention must be given to comparative pharmacokinetics and metabolism, likely exposure scenarios, possible mechanisms of action, and the potential role of arsenic as an essential nutrient.

  4. A review of toxicity studies of single-walled carbon nanotubes in laboratory animals.

    Science.gov (United States)

    Ema, Makoto; Gamo, Masashi; Honda, Kazumasa

    2016-02-01

    We summarized the findings of in vivo toxicity studies of single-walled carbon nanotubes (SWCNTs) in laboratory animals. The large majority addressed the pulmonary toxicity of SWCNTs in rodents. Inhalation, pharyngeal aspiration, and intratracheal instillation studies revealed that SWCNTs caused acute and chronic inflammation, granuloma formation, collagen deposition, fibrosis, and genotoxic effects in the lungs. Pulmonary toxicity of well-dispersed SWCNTs was more potent than less dispersed ones. Airway exposure to SWCNTs also induced cardiovascular diseases in mice. Oxidative stress was caused by the administration of SWCNTs. Injected SWCNTs were distributed throughout most of the organs including the brain, mainly retained in the lungs, liver, and spleen, and eliminated through the kidney and bile duct. Orally administered SWCNTs are suggested to be absorbed from the gastrointestinal tract to the blood circulation in mice and rats. Although no definitive study on the carcinogenicity of SWCNTs is available at present, evidence of carcinogenicity has not been reported in toxicity studies cited in this review. Overall, the available data provides initial information on SWCNT toxicity. To further clarify their toxicity and risk assessment, studies should be conducted using well-characterized SWCNTs, standard protocols, and the relevant route and doses of human exposure.

  5. Preclinical animal acute toxicity studies of new developed MRI contrast agent based on gadolinium

    Science.gov (United States)

    Nam, I. F.; Zhuk, V. V.

    2015-04-01

    Acute toxicity test of new developed MRI contrast agent based on disodium salt of gadopentetic acid complex were carried out on Mus musculus and Sprague Dawley rats according to guidelines of preclinical studies [1]. Groups of six animals each were selected for experiment. Death and clinical symptoms of animals were recorded during 14 days. As a result the maximum tolerated dose (MTD) for female mice is 2.8 mM/kg of body weight, male mice - 1.4 mM/kg, female rats - 2.8 mM/kg, male rats - 5.6 mM/kg of body weight. No Observed Adverse Effect Dose (NOAEL) for female mice is 1.4 mM/kg, male mice - 0.7 mM/kg, male and female rats - 0.7 mM/kg. According to experimental data new developed MRI contrast agent based on Gd-DTPA complex is low-toxic.

  6. Is Boric Acid Toxic to Reproduction in Humans? Assessment of the Animal Reproductive Toxicity Data and Epidemiological Study Results.

    Science.gov (United States)

    Duydu, Yalçın; Başaran, Nurşen; Ustündağ, Aylin; Aydın, Sevtap; Undeğer, Ulkü; Ataman, Osman Yavuz; Aydos, Kaan; Düker, Yalçın; Ickstadt, Katja; Waltrup, Brita Schulze; Golka, Klaus; Bolt, Hermann Maximilian

    2016-01-01

    Boric acid and sodium borates are classified as toxic to reproduction in the CLP Regulation under "Category 1B" with the hazard statement of "H360FD". This classification is based on the reprotoxic effects of boric acid and sodium borates in animal experiments at high doses. However, boron mediated reprotoxic effects have not been proven in epidemiological studies so far. The epidemiological study performed in Bandırma boric acid production plant is the most comprehensive published study in this field with 204 voluntarily participated male workers. Sperm quality parameters (sperm morphology, concentration and motility parameters), FSH, LH and testosterone levels were determined in all participated employees as the reproductive toxicity biomarkers of males. However, boron mediated unfavorable effects on reproduction in male workers have not been determined even in the workers under very high daily boron exposure (0.21 mg B/kg-bw/day) conditions. The NOAEL for rat reproductive toxicity is equivalent to a blood boron level of 2020 ng/g. This level is higher than the mean blood boron concentration (223.89 ± 69.49 ng/g) of the high exposure group workers in Bandırma boric acid production plant (Turkey) by a factor of 9. Accordingly, classifying boric acid and sodium borates under "Category 1B" as "presumed reproductive human toxicant in the CLP regulation seems scientifically not reasonable. The results of the epidemiological studies (including the study performed in China) support for a down-classification of boric acid from the category 1B, H360FD to category 2, H361d, (suspected of damaging the unborn child).

  7. Comprehensive toxicity study of safrole using a medium-term animal model with gpt delta rats.

    Science.gov (United States)

    Jin, M; Kijima, A; Suzuki, Y; Hibi, D; Inoue, T; Ishii, Y; Nohmi, T; Nishikawa, A; Ogawa, K; Umemura, T

    2011-12-18

    In order to investigate a medium-term animal model using reporter gene transgenic rodents in which general toxicity, genotoxicity and carcinogenicity are evaluated, F344 gpt delta rats were given a diet containing 0.1% and 0.5% (a carcinogenic dose) safrole for 13 weeks. Serum biochemistry and histopathological examinations revealed overt hepatotoxicity of safrole, in line with previous reports. In the current study, safrole treatment possibly resulted in renal toxicity in male rats. In the in vivo mutation assays, an increase or a tendency to increase of the gpt mutant frequencies (MFs) was observed in both sexes at the carcinogenic dose. The number and area of foci of glutathione S-transferase placental form (GST-P) positive hepatocytes, ratio of proliferating cell nuclear antigen (PCNA)-positive hepatocytes and 8-hydroxydeoxyguanosine (8-OHdG) levels in liver DNA were significantly increased in both sexes of the 0.5% group. The overall data suggested that the present model might be a promising candidate for investigating comprehensive toxicities of the agents. In addition, data demonstrating the base modification and cell proliferation due to exposure to safrole could contribute to understanding safrole-induced hepatocarcinogenesis, which imply expanding in application of this model.

  8. Utilization of animal studies to determine the effects and human risks of environmental toxicants (drugs, chemicals, and physical agents).

    Science.gov (United States)

    Brent, Robert L

    2004-04-01

    Toxicology studies using animals and in vitro cellular or tissue preparations have been used to study the toxic effects and mechanism of action of drugs and chemicals and to determine the effective and safe dose of drugs in humans and the risk of toxicity from chemical exposures. Studies in pregnant animals are used to determine the risk of birth defects and other reproductive effects. There is no question that whole animal teratology studies are helpful in raising concerns about the reproductive effects of drugs and chemicals, but negative animal studies do not guarantee that these agents are free from reproductive effects. There are examples in which drug testing was negative in animals (rat and mouse) but was teratogenic in the human (thalidomide), and there are examples in which a drug was teratogenic in an animal model but not in the human (diflunisal). Testing in animals could be improved if animal dosing using the mg/kg basis were abandoned and drugs and chemicals were administered to achieve pharmacokinetically equivalent serum levels in the animal and the human. Because most human teratogens have been discovered by alert physicians or epidemiology studies, not animal studies, animal studies play a minor role in discovering teratogens. In vitro studies play an even less important role, although they are helpful in describing the cellular or tissue effects of the drugs or chemicals. One cannot determine the magnitude of human risks from these in vitro studies. Performing toxicology studies on adult animals is performed by pharmaceutical companies, chemical companies, the Food and Drug Administration, many laboratories at the National Institutes of Health, and scientific investigators in laboratories throughout the world. Although a vast amount of animal toxicology studies are performed on pregnant animals and numerous toxicology studies are performed on adult animals, there is a paucity of animal studies using newborn, infant, and juvenile animals. This

  9. Statistical studies of animal response data from USF toxicity screening test method

    Science.gov (United States)

    Hilado, C. J.; Machado, A. M.

    1978-01-01

    Statistical examination of animal response data obtained using Procedure B of the USF toxicity screening test method indicates that the data deviate only slightly from a normal or Gaussian distribution. This slight departure from normality is not expected to invalidate conclusions based on theoretical statistics. Comparison of times to staggering, convulsions, collapse, and death as endpoints shows that time to death appears to be the most reliable endpoint because it offers the lowest probability of missed observations and premature judgements.

  10. A review of toxicity studies on graphene-based nanomaterials in laboratory animals.

    Science.gov (United States)

    Ema, Makoto; Gamo, Masashi; Honda, Kazumasa

    2017-04-01

    We summarized the findings of toxicity studies on graphene-based nanomaterials (GNMs) in laboratory mammals. The inhalation of graphene (GP) and graphene oxide (GO) induced only minimal pulmonary toxicity. Bolus airway exposure to GP and GO caused acute and subacute pulmonary inflammation. Large-sized GO (L-GO) was more toxic than small-sized GO (S-GO). Intratracheally administered GP passed through the air-blood barrier into the blood and intravenous GO distributed mainly in the lungs, liver, and spleen. S-GO and L-GO mainly accumulated in the liver and lungs, respectively. Limited information showed the potential behavioral, reproductive, and developmental toxicity and genotoxicity of GNMs. There are indications that oxidative stress and inflammation may be involved in the toxicity of GNMs. The surface reactivity, size, and dispersion status of GNMs play an important role in the induction of toxicity and biodistribution of GNMs. Although this review paper provides initial information on the potential toxicity of GNMs, data are still very limited, especially when taking into account the many different types of GNMs and their potential modifications. To fill the data gap, further studies should be performed using laboratory mammals exposed using the route and dose anticipated for human exposure scenarios.

  11. [Selenium toxicity in domestic animals].

    Science.gov (United States)

    Mihajlović, M

    1992-01-01

    The earliest written report of selenium poisoning is thought to be the description by Marco Polo of a necrotic hoof disease of horses that occurred in China in 13. century. However recognition of Se as toxic principle come in the early 1930s. Severity of Se poisoning depends on chemical forms of the element, species of animals and routes of administration. The soluble Se salts (Na2SeO3 and Na2SeO4) appear to be among the more toxic compounds; the Se inherent in grains and selenoamino acids (selenomethionine and selenocystine) appear to have relative moderate toxicity; the poorly soluble forms (e.g., elemental Se, Na2Se, SeS2 and diphenyl selenide) are among the least toxic of the Se compounds. In general, toxicity of Se compounds are substantially less when they are administered orally than when they are given parenterally. Rosenfeld and Beath described three clinical types of Se intoxication: acute selenosis, subacute selenosis (i.e., blind staggers type), and chronic selenosis (i.e., alkali disease type). Acute poisoning occurs when high Se content plants are consumed in large quantities within short period. Accidental acute poisoning occurs as consequence of errors in formulation of a Se supplemented diet. The most characteristic sign of acute selenosis is garlic breath due to the pulmonary excretion of volatile Se metabolites. Other signs include lethargy, excessive salivation, vomiting, dyspnea, muscle tremors and respiratory distress. Pathological findings are: congestion of the liver and kidney, fatty degeneration and focal necrosis of the liver, endocarditis and myocarditis. Subacute selenosis ("blind staggers") occurs as a consequence of exposure to large doses of Se over a longer period of time and manifests with neurological signs (e.g., blindness, ataxia, disorientation) and respiratory distress. This form of selenosis is most frequently observed in grazing animals that have consumed Se-accumulated plants. Chronic selenosis ("alkali disease") comes

  12. Evaluation of some in vitro tests to reduce and replace the sub-acute animal toxicity studies.

    Science.gov (United States)

    Chhabra, Rajendra S; Ress, Nancy B; Harbell, John W; Curren, Rodger D

    2004-06-01

    The toxicologic and carcinogenic potential of chemicals is usually determined through a sequence of acute, sub-acute (14-day), sub-chronic (90-day) and chronic (two-year) studies in rats and mice of both sexes. The US National Toxicology Program (NTP) does not conduct acute toxicity studies. Dose levels for 14-day toxicity studies are typically estimated from information in the literature, if available. The toxicology information obtained from 14-day studies is used in the selection of doses for 90-day studies. The protocol for 14-day studies consists of five doses and control groups and five animals per group of each sex and species, resulting in the use of 120 animals per study. At present, in addition to refining the current testing protocols, the NTP is evaluating the potential for in vitro test methods to partially or completely avoid the need for 14-day toxicity studies, especially for chemicals where the dermal route of exposure is used. The in vitro assays used were the EpiDerm bioassay to estimate dermal irritation, the neutral red uptake (NRU) bioassay to estimate systemic toxicity and the primary rat hepatocyte cytotoxicity (PRHC) assay to estimate hepatotoxicity. The purpose of using these assays was to assess their potential for predicting relative in vivo toxicity and to support dose selection decisions for 90-day studies. In general, based on these limited number of studies, the EpiDerm and NRU tests were predictive of the responses observed in in vivo studies. However, a larger comparative database is needed to derive definitive conclusions regarding the value of in vitro tests in the prediction of in vivo effects.

  13. The Historical Development of Animal Toxicity Testing

    OpenAIRE

    Gertler, N

    1997-01-01

    This paper traces the historical development of animal toxicity testing, from its ancient origins through the period of standardization following World War II. It explores the roots of toxicity testing in physiology and experimental medicine, drug development, and the detection and identification of poisons. The discussion then turns to the shift in focus from acute to chronic toxicity which occurred around the turn of the century. The controversy over the potential toxicity of preservatives ...

  14. Improved dispersion method of multi-wall carbon nanotube for inhalation toxicity studies of experimental animals.

    Science.gov (United States)

    Taquahashi, Yuhji; Ogawa, Yukio; Takagi, Atsuya; Tsuji, Masaki; Morita, Koichi; Kanno, Jun

    2013-01-01

    A multi-wall carbon nanotube (MWCNT) product Mitsui MWNT-7 is a mixture of dispersed single fibers and their agglomerates/aggregates. In rodents, installation of such mixture induces inflammatory lesions triggered predominantly by the aggregates/agglomerates at the level of terminal bronchiole of the lungs. In human, however, pulmonary toxicity induced by dispersed single fibers that reached the lung alveoli is most important to assess. Therefore, a method to generate aerosol predominantly consisting of dispersed single fibers without changing their length and width is needed for inhalation studies. Here, we report a method (designated as Taquann method) to effectively remove the aggregate/agglomerates and enrich the well-dispersed singler fibers in dry state without dispersant and without changing the length and width distribution of the single fibers. This method is base on two major concept; liquid-phase fine filtration and critical point drying to avoid re-aggregation by surface tension. MWNT-7 was suspended in Tert-butyl alcohol, freeze-and-thawed, filtered by a vibrating 25 µm mesh Metallic Sieve, snap-frozen by liquid nitrogen, and vacuum-sublimated (an alternative method to carbon dioxide critical point drying). A newly designed direct injection system generated well-dispersed aerosol in an inhalation chamber. The lung of mice exposed to the aerosol contained single fibers with a length distribution similar to the original and the Taquann-treated sample. Taquann method utilizes inexpensive materials and equipments mostly found in common biological laboratories, and prepares dry powder ready to make well-dispersed aerosol. This method and the chamber with direct injection system would facilitate the inhalation toxicity studies more relevant to human exposure.

  15. Implications of Animal Welfare on Toxicity Testing

    DEFF Research Database (Denmark)

    Meyer, Otto A.

    1993-01-01

    The testing strategy for chemical substances is discussed with regard to obtaining improved quality of data for health assessment while respecting the ethical responsibility for consideration of the welfare of the animals involved. Ensuring animal welfare without indulging too much...... in anthropomorphism leads to better research/testing. Current trends in toxicity testing will result in tests involving more sophisticated techniques, better quality of laboratory animals, and eventually the use of fewer animals....

  16. Toxic Effects of Cannabis and Cannabinoids: Animal Data

    Directory of Open Access Journals (Sweden)

    Pierre Beaulieu

    2005-01-01

    Full Text Available The present article reviews the main toxic effects of cannabis and cannabinoids in animals. Toxic effects can be separated into acute and chronic classifications. Acute toxicity studies show that it is virtually impossible to die from acute administration of marijuana or tetrahydrocannabinol, the main psychoactive component of cannabis. Chronic toxicity involves lesions of airway and lung tissues, as well as problems of neurotoxicity, tolerance and dependence, and dysregulations in the immune and hormonal systems. Animal toxicity data, however, are difficult to extrapolate to humans.

  17. Efficacy and safety/toxicity study of recombinant vaccinia virus JX-594 in two immunocompetent animal models of glioma.

    Science.gov (United States)

    Lun, XueQing; Chan, Jennifer; Zhou, Hongyuan; Sun, Beichen; Kelly, John J P; Stechishin, Owen Owen; Bell, John C; Parato, Kelley; Hu, Kang; Vaillant, Dominique; Wang, Jiahu; Liu, Ta-Chiang; Breitbach, Caroline; Kirn, David; Senger, Donna L; Forsyth, Peter A

    2010-11-01

    The purpose of this study was to investigate the oncolytic potential of the recombinant, granulocyte macrophage colony-stimulating factor (GM-CSF)-expressing vaccinia virus (VV) JX-594 in experimental malignant glioma (MGs) in vitro and in immunocompetent rodent models. We have found that JX-594 killed all MG cell lines tested in vitro. Intratumoral (i.t.) administration of JX-594 significantly inhibited tumor growth and prolonged survival in rats-bearing RG2 intracranial (i.c.) tumors and mice-bearing GL261 brain tumors. Combination therapy with JX-594 and rapamycin significantly increased viral replication and further prolonged survival in both immunocompetent i.c. MG models with several animals considered "cured" (three out of seven rats >120 days, terminated experiment). JX-594 infected and killed brain tumor-initiating cells (BTICs) from patient samples grown ex vivo, and did so more efficiently than other oncolytic viruses MYXV, Reovirus type-3, and VSV(ΔM51). Additional safety/toxicity studies in nontumor-bearing rodents treated with a supratherapeutic dose of JX-594 demonstrated GM-CSF-dependent inflammation and necrosis. These results suggest that i.c. administered JX-594 triggers a predictable GM-CSF-mediated inflammation in murine models. Before proceeding to clinical trials, JX-594 should be evaluated in the brains of nonhuman primates and optimized for the viral doses, delivery routes as well as the combination agents (e.g., mTOR inhibitors).

  18. Animal alternatives for whole effluent toxicity testing ...

    Science.gov (United States)

    Since the 1940s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that toxicity based effluent assessments and subsequent discharge controls became globally important, when it was recognized that physical and chemical measurements alone did not protect the environment from potential impacts. Consequently, various strategies using different toxicity tests, whole effluent assessment techniques (incorporating bioaccumulation potential and persistence) plus supporting analytical tools have been developed over 30 years of practice. Numerous workshops and meetings have focused on effluent risk assessment through ASTM, SETAC, OSPAR, UK competent authorities, and EU specific country rules. Concurrent with this drive to improve effluent quality using toxicity tests, interest in reducing animal use has risen. The Health and Environmental Sciences Institute (HESI) organized and facilitated an international workshop in March 2016 to evaluate strategies for concepts, tools, and effluent assessments and update the toolbox of for effluent testing methods. The workshop objectives were to identify opportunities to use a suite of strategies for effluents, and to identify opportunities to reduce the reliance on animal tests and to determine barriers to implementation of new methodologie

  19. Animal alternatives for whole effluent toxicity testing ...

    Science.gov (United States)

    Since the 1940s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that toxicity based effluent assessments and subsequent discharge controls became globally important, when it was recognized that physical and chemical measurements alone did not protect the environment from potential impacts. Consequently, various strategies using different toxicity tests, whole effluent assessment techniques (incorporating bioaccumulation potential and persistence) plus supporting analytical tools have been developed over 30 years of practice. Numerous workshops and meetings have focused on effluent risk assessment through ASTM, SETAC, OSPAR, UK competent authorities, and EU specific country rules. Concurrent with this drive to improve effluent quality using toxicity tests, interest in reducing animal use has risen. The Health and Environmental Sciences Institute (HESI) organized and facilitated an international workshop in March 2016 to evaluate strategies for concepts, tools, and effluent assessments and update the toolbox of for effluent testing methods. The workshop objectives were to identify opportunities to use a suite of strategies for effluents, and to identify opportunities to reduce the reliance on animal tests and to determine barriers to implementation of new methodologie

  20. Non-animal Replacements for Acute Toxicity Testing.

    Science.gov (United States)

    Barker-Treasure, Carol; Coll, Kevin; Belot, Nathalie; Longmore, Chris; Bygrave, Karl; Avey, Suzanne; Clothier, Richard

    2015-07-01

    Current approaches to predicting adverse effects in humans from acute toxic exposure to cosmetic ingredients still heavily necessitate the use of animals under EU legislation, particularly in the context of the REACH system, when cosmetic ingredients are also destined for use in other industries. These include the LD50 test, the Up-and-Down Procedure and the Fixed Dose Procedure, which are regarded as having notable scientific deficiencies and low transferability to humans. By expanding on previous in vitro tests, such as the animal cell-based 3T3 Neutral Red Uptake (NRU) assay, this project aims to develop a truly animal-free predictive test for the acute toxicity of cosmetic ingredients in humans, by using human-derived cells and a prediction model that does not rely on animal data. The project, funded by Innovate UK, will incorporate the NRU assay with human dermal fibroblasts in animal product-free culture, to generate an in vitro protocol that can be validated as an accepted replacement for the currently available in vivo tests. To date, the project has successfully completed an assessment of the robustness and reproducibility of the method, by using sodium lauryl sulphate (SLS) as a positive control, and displaying analogous results to those of the original studies with mouse 3T3 cells. Currently, the testing of five known ingredients from key groups (a surfactant, a preservative, a fragrance, a colour and an emulsifier) is under way. The testing consists of initial range-finding runs followed by three valid runs of a main experiment with the appropriate concentration ranges, to generate IC50 values. Expanded blind trials of 20 ingredients will follow. Early results indicate that this human cell-based test holds the potential to replace aspects of in vivo animal acute toxicity testing, particularly with reference to cosmetic ingredients. 2015 FRAME.

  1. Acute and Subacute Toxicity study of the Acetone Leaf extract of Centella asiatica in Experimental Animal Models

    Institute of Scientific and Technical Information of China (English)

    PK Chauhan; V Singh

    2012-01-01

    Objective: To evaluate acute and subacute toxicity of the acetone extract of Centella asiatica (Brahmi). Methods: Toxicity of Centella asiatica was evaluated in Swiss mice after ingestion of the extract during one day (acute model) and during 15 days (subacute model). The Biochemical parameters evaluated included creatinine, calcium, inorganic phosphorous, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were assessed using commercial kits. Results: The results of the present investigation revealed that the LD50 of the extract is higher than 4000mg/kg and subacute treatment did not shows any change in corporal weight and hematological parameters. However, a change in liver weight but not in hepatic enzymes was observed. This suggested that the liver function is not altered by Centella asiatica. Some changes in the creatinine content were observed but could not be relative with the extract dose.Conclusions:The results suggest that the plant seems to be destitute of toxic effects in mice.

  2. Developmental toxicity of indium: embryotoxicity and teratogenicity in experimental animals.

    Science.gov (United States)

    Nakajima, Mikio; Usami, Makoto; Nakazawa, Ken; Arishima, Kazuyoshi; Yamamoto, Masako

    2008-12-01

    Indium, a precious metal classified in group 13 (IIIB) in the periodic table, has been used increasingly in the semiconductor industry. Because indium is a rare metal, technology for indium recycling from transparent conducting films for liquid crystal displays is desired, and its safety evaluation is becoming increasingly necessary. The developmental toxicity of indium in experimental animals was summarized. The intravenous or oral administration of indium to pregnant animals causes growth inhibition and the death of embryos in hamsters, rats, and mice. The intravenous administration of indium to pregnant animals causes embryonic or fetal malformation, mainly involving digit and tail deformities, in hamsters and rats. The oral administration of indium also induces fetal malformation in rats and rabbits, but requires higher doses. No teratogenicity has been observed in mice. Caudal hypoplasia, probably due to excessive cell loss by increased apoptosis in the tailbud, in the early postimplantation stage was considered to account for indium-induced tail malformation as a possible pathogenetic mechanism. Findings from in vitro experiments indicated that the embryotoxicity of indium could have direct effects on the conceptuses. Toxicokinetic studies showed that the embryonic exposure concentration was more critical than the exposure time regarding the embryotoxicity of indium. It is considered from these findings that the risk of the developmental toxicity of indium in humans is low, unless an accidentally high level of exposure or unknown toxic interaction occurs because of possible human exposure routes and levels (i.e. oral, very low-level exposure).

  3. Non-animal methodologies within biomedical research and toxicity testing.

    Science.gov (United States)

    Knight, Andrew

    2008-01-01

    Laboratory animal models are limited by scientific constraints on human applicability, and increasing regulatory restrictions, driven by social concerns. Reliance on laboratory animals also incurs marked - and in some cases, prohibitive - logistical challenges, within high-throughput chemical testing programmes, such as those currently underway within Europe and the US. However, a range of non-animal methodologies is available within biomedical research and toxicity testing. These include: mechanisms to enhance the sharing and assessment of existing data prior to conducting further studies, and physicochemical evaluation and computerised modelling, including the use of structure-activity relationships and expert systems. Minimally-sentient animals from lower phylogenetic orders or early developmental vertebral stages may be used, as well as microorganisms and higher plants. A variety of tissue cultures, including immortalised cell lines, embryonic and adult stem cells, and organotypic cultures, are also available. In vitro assays utilising bacterial, yeast, protozoal, mammalian or human cell cultures exist for a wide range of toxic and other endpoints. These may be static or perfused, and may be used individually, or combined within test batteries. Human hepatocyte cultures and metabolic activation systems offer potential assessment of metabolite activity and organ-organ interaction. Microarray technology may allow genetic expression profiling, increasing the speed of toxin detection, well prior to more invasive endpoints. Enhanced human clinical trials utilising micro- dosing, staggered dosing, and more representative study populations and durations, as well as surrogate human tissues, advanced imaging modalities and human epidemiological, sociological and psycho- logical studies, may increase our understanding of illness aetiology and pathogenesis, and facilitate the development of safe and effective pharmacologic interventions. Particularly when human tissues

  4. Pyridostigmine Synergistic Toxicity Study.

    Science.gov (United States)

    1995-05-31

    AND DEET IN THE LABORATORY RAT 1. Executive Sum m ary .............................................................................................. 2 2...TOXICOLOGICAL STUDY 75-48-2665 ACUTE ORAL TOXICITY STUDY OF PYRIDOSTIGMINE BROMIDE. PERMETHRIN. AND DEET IN THE LABORATORY RAT 1. REFERENCES: See Appendix A... LABORATORY RAT 1. PURPOSE: The purpose of this study was to determine potential toxic interactions when pyridostigmine bromide. permethrin. and DEET are given

  5. Neurochemical and Behavioral Characteristics of Toxic Milk Mice: An Animal Model of Wilson’s Disease

    OpenAIRE

    2013-01-01

    Toxic milk mice have an inherited defect of copper metabolism. Hepatic phenotype of the toxic milk mice is similar to clinical findings in humans suffering from Wilson’s disease (WND). In the present study, neurotransmitter system and locomotor performance in toxic milk mice was examined to verify the feasibility of this animal model for studying neuropathology of WND. Mice aged 2 and 12 months were used in the experiment. The mice were tested according to rotarod and footprint protocols. Mon...

  6. Animal models of peripheral neuropathy due to environmental toxicants.

    Science.gov (United States)

    Rao, Deepa B; Jortner, Bernard S; Sills, Robert C

    2014-01-01

    Despite the progress in our understanding of pathogeneses and the identification of etiologies of peripheral neuropathy, idiopathic neuropathy remains common. Typically, attention to peripheral neuropathies resulting from exposure to environmental agents is limited relative to more commonly diagnosed causes of peripheral neuropathy (diabetes and chemotherapeutic agents). Given that there are more than 80,000 chemicals in commerce registered with the Environmental Protection Agency and that at least 1000 chemicals are known to have neurotoxic potential, very few chemicals have been established to affect the peripheral nervous system (mainly after occupational exposures). A wide spectrum of exposures, including pesticides, metals, solvents, nutritional sources, and pharmaceutical agents, has been related, both historically and recently, to environmental toxicant-induced peripheral neuropathy. A review of the literature shows that the toxicity and pathogeneses of chemicals adversely affecting the peripheral nervous system have been studied using animal models. This article includes an overview of five prototypical environmental agents known to cause peripheral neuropathy--namely, organophosphates, carbon disulfide, pyridoxine (Vitamin B6), acrylamide, and hexacarbons (mainly n-hexane, 2,5-hexanedione, methyl n-butyl ketone). Also included is a brief introduction to the structural components of the peripheral nervous system and pointers on common methodologies for histopathologic evaluation of the peripheral nerves.

  7. Safety assessment of DHA-rich microalgae from Schizochytrium sp. Part V: target animal safety/toxicity study in growing swine.

    Science.gov (United States)

    Abril, Ruben; Garrett, Jack; Zeller, Samuel G; Sander, Wayne J; Mast, Richard W

    2003-02-01

    The purpose of this study was to determine the potential toxicity of docosahexaenoic acid (DHA)-rich microalgae (DRM) from Schizochytrium sp., administered in the diet of growing swine. DRM was administered in the diet to groups of castrated male growing pigs (mixed commercial breeds, Landrace & Large White) reared from early weaned (weighing approximately 20 lbs) to approximately 250-270 lbs. Over the course of the 120 day study, animals were fed ad libitum four DRM treatment diets, each designed to optimize weight gain over the growing cycle, and a control diet. DRM was incorporated into the diet of the first treatment group at a level delivering 2.680 kg DRM per pig over the course of 120 days (a constant, whole-life exposure) equating to 598 g DHA per pig. DRM was incorporated into finisher diets only (administered over the last 42 days of the growing cycle) to treatment groups 2, 3, and 4 delivering 1.169, 3.391, and 5.746 kg DRM per pig (261, 756, and 1281 g DHA per pig). These levels represent approximately 1, 3, and 5 times the anticipated commercial dose and were delivered in a feeding strategy designed to mimic commercial use. Vitamin E was added to all diet groups to provide supplementary dietary antioxidant given the high content of polyunsaturated fat in DRM. There were no statistically significant treatment-related effects in clinical observations, body weights, food consumption, mortality, hematologic values, gross necropsy findings, organ weights or histopathology. The only DRM treatment-related changes were higher weight gain and feed conversion efficiency, anticipated results based on the increased fat content in the experimental DRM treatments. This study demonstrates that administration of DRM (at up to five times the anticipated commercial dose) did not produce any treatment-related adverse effects in commercial strains of swine.

  8. Molecular Mechanisms of Microcystin Toxicity in Animal Cells

    Directory of Open Access Journals (Sweden)

    Alexandre Campos

    2010-01-01

    Full Text Available Microcystins (MC are potent hepatotoxins produced by the cyanobacteria of the genera Planktothrix, Microcystis, Aphanizomenon, Nostoc and Anabaena. These cyclic heptapeptides have strong affinity to serine/threonine protein phosphatases (PPs thereby acting as an inhibitor of this group of enzymes. Through this interaction a cascade of events responsible for the MC cytotoxic and genotoxic effects in animal cells may take place. Moreover MC induces oxidative stress in animal cells and together with the inhibition of PPs, this pathway is considered to be one of the main mechanisms of MC toxicity. In recent years new insights on the key enzymes involved in the signal-transduction and toxicity have been reported demonstrating the complexity of the interaction of these toxins with animal cells. Key proteins involved in MC up-take, biotransformation and excretion have been identified, demonstrating the ability of aquatic animals to metabolize and excrete the toxin. MC have shown to interact with the mitochondria. The consequences are the dysfunction of the organelle, induction of reactive oxygen species (ROS and cell apoptosis. MC activity leads to the differential expression/activity of transcriptional factors and protein kinases involved in the pathways of cellular differentiation, proliferation and tumor promotion activity. This activity may result from the direct inhibition of the protein phosphatases PP1 and PP2A. This review aims to summarize the increasing data regarding the molecular mechanisms of MC toxicity in animal systems, reporting for direct MC interacting proteins and key enzymes in the process of toxicity biotransformation/excretion of these cyclic peptides.

  9. Studies on the effect of 4-methylpyrazole on methanol poisoning using the monkey as an animal model: with particular reference to the ocular toxicity.

    Science.gov (United States)

    Blomstrand, R; Ingemansson, S O

    1984-07-01

    Young cynomolgus monkeys (Macaca fascicularis) were chosen as a model to investigate the ocular toxicity in animals poisoned with methanol and treated with 4-methylpyrazole (4-MP). The metabolism of methanol in the monkey was investigated after administration of 4-MP. Plasma levels of methanol, formic acid, 4-MP and 4-hydroxy-MP (4-OH-MP) were determined. After intramuscular injection, 4-MP was rapidly absorbed and depressed the elimination rate of methanol as well as the accumulation of formate in the blood. The results show the same great individual variations in monkeys as in humans regarding the susceptibility to methanol poisoning. Administration of a single dose of 5 g/kg induces a serious intoxication in most monkeys, causing death to some of them. Two monkeys receiving a single dose of 6 g/kg of methanol developed a serious initial inebriation and were treated with 4-MP. These monkeys survived and showed no signs of toxicity on ocular examinations which included ophtalmoscopy and electroretinogram (ERG) recordings.

  10. Green Biosynthesis, Characterization, In vitro Antidiabetic Activity, and Investigational Acute Toxicity Studies of Some Herbal-mediated Silver Nanoparticles on Animal Models.

    Science.gov (United States)

    Shanker, Kalakotla; Mohan, Gottumukkala Krishna; Hussain, Md Ashwaq; Jayarambabu, Naradala; Pravallika, Poka Lakshmi

    2017-01-01

    Diabetes is a metabolic disorder characterized by hyperglycemia, altered carbohydrate, lipid and protein metabolism. In recent studies, Nanoscience and nanotechnology are blazing fields for researchers; for researchers; of late there has been a prodigious excitement in the field of nanopharmacology to study silver nanoparticle (SNP) synthesis using natural products. Biological methods have been used to synthesize SNPs using medicinally active plants having an antidiabetic role, and this made us to assess the biologically synthesized SNPs from the seed extract of Psoralea corylifolia using 1 mM silver nitrate solution. The synthesized herbal-mediated SNPs (HMSNPs) were subjected to various characterization techniques such as X-ray diffraction analysis (XRD), energy dispersive X-ray (EDX) analysis, transmission electron microscope (TEM), and differential light scattering (DLS), respectively. In the current study the HMSNPs were tested to observe the in vitro antidiabetic activity and possible toxic effects in healthy female albino mice by following OECD guidelines-425. Huge data from biochemical, cellular, mouse, and chemical inhibitor studies have recognized protein tyrosine phosphatase 1B (PTP1B) as a major negative regulator of insulin signaling. In addition, corroboration suggests that insulin action can be enhanced by the inhibition of PTP1B. Keeping in view of the above fact, the PTP1B assay was done to determine the PTP1 B inhibitory effect of HMSNPs. It can be concluded that medicinal plants can be a good source for the synthe sis of HMSNPs. This study can be used for the development of valuable nanomedicines to treat various ailments, and it also highlights the safety and biocompatibility of SNPs within a biological cell; in vivo parameters need to be considered for further discoveries. In present research, acute oral toxicity studies and in vitro anti diabetic activity of Herbal mediated silver nanoparticles (HMSNPs) has been investigated. Characterization

  11. Green Biosynthesis, Characterization, In vitro Antidiabetic Activity, and Investigational Acute Toxicity Studies of Some Herbal-mediated Silver Nanoparticles on Animal Models

    Science.gov (United States)

    Shanker, Kalakotla; Mohan, Gottumukkala Krishna; Hussain, Md. Ashwaq; Jayarambabu, Naradala; Pravallika, Poka Lakshmi

    2017-01-01

    Diabetes is a metabolic disorder characterized by hyperglycemia, altered carbohydrate, lipid and protein metabolism. In recent studies, Nanoscience and nanotechnology are blazing fields for researchers; for researchers; of late there has been a prodigious excitement in the field of nanopharmacology to study silver nanoparticle (SNP) synthesis using natural products. Biological methods have been used to synthesize SNPs using medicinally active plants having an antidiabetic role, and this made us to assess the biologically synthesized SNPs from the seed extract of Psoralea corylifolia using 1 mM silver nitrate solution. The synthesized herbal-mediated SNPs (HMSNPs) were subjected to various characterization techniques such as X-ray diffraction analysis (XRD), energy dispersive X-ray (EDX) analysis, transmission electron microscope (TEM), and differential light scattering (DLS), respectively. In the current study the HMSNPs were tested to observe the in vitro antidiabetic activity and possible toxic effects in healthy female albino mice by following OECD guidelines-425. Huge data from biochemical, cellular, mouse, and chemical inhibitor studies have recognized protein tyrosine phosphatase 1B (PTP1B) as a major negative regulator of insulin signaling. In addition, corroboration suggests that insulin action can be enhanced by the inhibition of PTP1B. Keeping in view of the above fact, the PTP1B assay was done to determine the PTP1 B inhibitory effect of HMSNPs. It can be concluded that medicinal plants can be a good source for the synthe sis of HMSNPs. This study can be used for the development of valuable nanomedicines to treat various ailments, and it also highlights the safety and biocompatibility of SNPs within a biological cell; in vivo parameters need to be considered for further discoveries. SUMMARY In present research, acute oral toxicity studies and in vitro anti diabetic activity of Herbal mediated silver nanoparticles (HMSNPs) has been investigated

  12. Animal models of disease: feline hyperthyroidism: an animal model for toxic nodular goiter.

    Science.gov (United States)

    Peterson, Mark E

    2014-11-01

    Since first discovered just 35 years ago, the incidence of spontaneous feline hyperthyroidism has increased dramatically to the extent that it is now one of the most common disorders seen in middle-aged to senior domestic cats. Hyperthyroid cat goiters contain single or multiple autonomously (i.e. TSH-independent) functioning and growing thyroid nodules. Thus, hyperthyroidism in cats is clinically and histologically similar to toxic nodular goiter in humans. The disease in cats is mechanistically different from Graves' disease, because neither the hyperfunction nor growth of these nodules depends on extrathyroidal circulating stimulators. The basic lesion appears to be an excessive intrinsic growth capacity of some thyroid cells, but iodine deficiency, other nutritional goitrogens, or environmental disruptors may play a role in the disease pathogenesis. Clinical features of feline toxic nodular goiter include one or more palpable thyroid nodules, together with signs of hyperthyroidism (e.g. weight loss despite an increased appetite). Diagnosis of feline hyperthyroidism is confirmed by finding the increased serum concentrations of thyroxine and triiodothyronine, undetectable serum TSH concentrations, or increased thyroid uptake of radioiodine. Thyroid scintigraphy demonstrates a heterogeneous pattern of increased radionuclide uptake, most commonly into both thyroid lobes. Treatment options for toxic nodular goiter in cats are similar to that used in humans and include surgical thyroidectomy, radioiodine, and antithyroid drugs. Most authorities agree that ablative therapy with radioiodine is the treatment of choice for most cats with toxic nodular goiter, because the animals are older, and the disease will never go into remission.

  13. A review of reproductive and developmental toxicity of silver nanoparticles in laboratory animals.

    Science.gov (United States)

    Ema, Makoto; Okuda, Hirokazu; Gamo, Masashi; Honda, Kazumasa

    2017-01-01

    We summarized significant effects reported in the literature on the reproductive and developmental toxicity of silver nanoparticles (AgNPs) in laboratory animals. AgNPs showed testicular/sperm toxicity in males and ovarian and embryonic toxicity in females. Maternal injection of AgNPs delayed physical development and impaired cognitive behavior in offspring. Ag was accumulated in the testes after administration of AgNPs. AgNPs were identified in the visceral yolk sac after administration during early gestation in mice. Radiolabeled AgNPs were detected in placenta, breast milk, and pre- and postnatal offspring after injection during late gestation in rats. Ag in the ionic form, and possibly also particles, was suggested to be bioavailable. Although this review provides initial information on the potential reproductive and developmental toxicity of AgNPs, data is still very limited. Further studies using state-of-the-art methodologies and the relevant routes and doses for human exposure are required.

  14. Using Online Tool (iPrior) for Modeling ToxCast™ Assays Towards Prioritization of Animal Toxicity Testing.

    Science.gov (United States)

    Abdelaziz, Ahmed; Sushko, Yurii; Novotarskyi, Sergii; Körner, Robert; Brandmaier, Stefan; Tetko, Igor V

    2015-01-01

    The use of long-term animal studies for human and environmental toxicity estimation is more discouraged than ever before. Alternative models for toxicity prediction, including QSAR studies, are gaining more ground. A recent approach is to combine in vitro chemical profiling and in silico chemical descriptors with the knowledge about toxicity pathways to derive a unique signature for toxicity endpoints. In this study we investigate the ToxCast™ Phase I data regarding their ability to predict long-term animal toxicity. We investigated thousands of models constructed in an effort to predict 61 toxicity endpoints using multiple descriptor packages and hundreds of in vitro assays. We investigated the use of in vitro assays and biochemical pathways on model performance. We identified 10 toxicity endpoints where biologically derived descriptors from in vitro assays or pathway perturbations improved the model prediction ability. In vivo toxicity endpoints proved generally challenging to model. Few models were possible to readily model with a balanced accuracy (BA) above 0.7. We also constructed in silico models to predict the outcome of 144 in vitro assays. This showed better statistical metrics with 79 out of 144 assays having median balanced accuracy above 0.7. This suggests that the in vitro datasets have a better modelability than in vivo animal toxicities for the given datasets. Moreover, we published an online platform (http://iprior.ochem.eu) that automates large-scale model building and analysis.

  15. Animal Studies of Addictive Behavior

    OpenAIRE

    Vanderschuren, Louk J.M.J.; Ahmed, Serge H.

    2013-01-01

    It is increasingly recognized that studying drug taking in laboratory animals does not equate to studying genuine addiction, characterized by loss of control over drug use. This has inspired recent work aimed at capturing genuine addiction-like behavior in animals. In this work, we summarize empirical evidence for the occurrence of several DSM-IV-like symptoms of addiction in animals after extended drug use. These symptoms include escalation of drug use, neurocognitive deficits, resistance to...

  16. Bias During the Evaluation of Animal Studies?

    Directory of Open Access Journals (Sweden)

    Andrew Knight

    2012-02-01

    Full Text Available My recent book entitled The Costs and Benefits of Animal Experiments seeks to answer a key question within animal ethics, namely: is animal experimentation ethically justifiable? Or, more precisely, is it justifiable within the utilitarian cost:benefit framework that fundamentally underpins most regulations governing animal experimentation? To answer this question I reviewed more than 500 scientific publications describing animal studies, animal welfare impacts, and alternative research, toxicity testing and educational methodologies. To minimise bias I focused primarily on large-scale systematic reviews that had examined the human clinical and toxicological utility of animal studies. Despite this, Dr. Susanne Prankel recently reviewed my book in this journal, essentially accusing me of bias. However, she failed to provide any substantive evidence to refute my conclusions, let alone evidence of similar weight to that on which they are based. Those conclusions are, in fact, firmly based on utilitarian ethical reasoning, informed by scientific evidence of considerable strength, and I believe they are robust.

  17. Toxicity of Nanoparticles on the Reproductive System in Animal Models: A Review

    Directory of Open Access Journals (Sweden)

    Rahim Dad Brohi

    2017-09-01

    Full Text Available In the last two decades, nanotechnologies demonstrated various applications in different fields, including detection, sensing, catalysis, electronics, and biomedical sciences. However, public concerns regarding the well-being of human may hinder the wide utilization of this promising innovation. Although, humans are exposed to airborne nanosized particles from an early age, exposure to such particles has risen dramatically within the last century due to anthropogenic sources of nanoparticles. The wide application of nanomaterials in industry, consumer products, and medicine has raised concerns regarding the potential toxicity of nanoparticles in humans. In this review, the effects of nanomaterials on the reproductive system in animal models are discussed. Females are particularly more vulnerable to nanoparticle toxicity, and toxicity in this population may affect reproductivity and fetal development. Moreover, various types of nanoparticles have negative impacts on male germ cells, fetal development, and the female reproductive system. These impacts are associated with nanoparticle modification, composition, concentration, route of administration, and the species of the animal. Therefore, understanding the impacts of nanoparticles on animal growth and reproduction is essential. Many studies have examined the effects of nanoparticles on primary and secondary target organs, with a concentration on the in vivo and in vitro effects of nanoparticles on the male and female reproductive systems at the clinical, cellular, and molecular levels. This review provides important information regarding organism safety and the potential hazards of nanoparticle use and supports the application of nanotechnologies by minimizing the adverse effects of nanoparticles in vulnerable populations.

  18. Towards An Advanced Graphene-Based Magnetic Resonance Imaging Contrast Agent: Sub-acute Toxicity and Efficacy Studies in Small Animals.

    Science.gov (United States)

    Kanakia, Shruti; Toussaint, Jimmy; Hoang, Dung Minh; Mullick Chowdhury, Sayan; Lee, Stephen; Shroyer, Kenneth R; Moore, William; Wadghiri, Youssef Z; Sitharaman, Balaji

    2015-12-02

    Current clinical Gd(3+)-based T1 magnetic resonance imaging (MRI) contrast agents (CAs) are suboptimal or unsuitable, especially at higher magnetic fields (>1.5 Tesla) for advanced MRI applications such as blood pool, cellular and molecular imaging. Herein, towards the goal of developing a safe and more efficacious high field T1 MRI CA for these applications, we report the sub-acute toxicity and contrast enhancing capabilities of a novel nanoparticle MRI CA comprising of manganese (Mn(2+)) intercalated graphene nanoparticles functionalized with dextran (hereafter, Mangradex) in rodents. Sub-acute toxicology performed on rats intravenously injected with Mangradex at 1, 50 or 100 mg/kg dosages 3 times per week for three weeks indicated that dosages ≤50 mg/kg could serve as potential diagnostic doses. Whole body 7 Tesla MRI performed on mice injected with Mangradex at a potential diagnostic dose (25 mg/kg or 455 nanomoles Mn(2+)/kg; ~2 orders of magnitude lower than the paramagnetic ion concentration in a typical clinical dose) showed persistent (up to at least 2 hours) contrast enhancement in the vascular branches (Mn(2+) concentration in blood at steady state = 300 ppb, per voxel = 45 femtomoles). The results lay the foundations for further development of Mangradex as a vascular and cellular/ molecular MRI probe.

  19. Animal language studies: What happened?

    Science.gov (United States)

    Pepperberg, Irene M

    2017-02-01

    The extent to which nonhuman animals can learn actual human language is a controversial question, but many nonhuman species have acquired elements of a two-way communication system that is, and was, sophisticated enough to enable its use in evaluating cognitive capacities. This article is a personal view of the history of these animal language studies.

  20. Bias During the Evaluation of Animal Studies?

    Science.gov (United States)

    Knight, Andrew

    2012-01-01

    Simple Summary Animal experimentation evokes strong emotional responses in people on both sides of the debate surrounding its ethical status. However, the true level of its usefulness to society may only be discerned by careful examination of reliable scientific evidence. My recent book, The Costs and Benefits of Animal Experiments, reviewed more than 500 relevant scientific publications. Recently in this journal, however, a reviewer essentially accused me of bias. Yet the conclusions of my book are based on sound reasoning and strong evidence, and no critic has yet provided any substantive evidence to refute them. Abstract My recent book entitled The Costs and Benefits of Animal Experiments seeks to answer a key question within animal ethics, namely: is animal experimentation ethically justifiable? Or, more precisely, is it justifiable within the utilitarian cost:benefit framework that fundamentally underpins most regulations governing animal experimentation? To answer this question I reviewed more than 500 scientific publications describing animal studies, animal welfare impacts, and alternative research, toxicity testing and educational methodologies. To minimise bias I focused primarily on large-scale systematic reviews that had examined the human clinical and toxicological utility of animal studies. Despite this, Dr. Susanne Prankel recently reviewed my book in this journal, essentially accusing me of bias. However, she failed to provide any substantive evidence to refute my conclusions, let alone evidence of similar weight to that on which they are based. Those conclusions are, in fact, firmly based on utilitarian ethical reasoning, informed by scientific evidence of considerable strength, and I believe they are robust. PMID:26486779

  1. Green biosynthesis, characterization, in vitro antidiabetic activity, and investigational acute toxicity studies of some herbal-mediated silver nanoparticles on animal models

    National Research Council Canada - National Science Library

    Kalakotla Shanker; Gottumukkala Krishna Mohan; Md Hussain; Naradala Jayarambabu; Poka Lakshmi Pravallika

    2017-01-01

    .... In recent studies, Nanoscience and nanotechnology are blazing fields for researchers; for researchers; of late there has been a prodigious excitement in the field of nanopharmacology to study silver nanoparticle...

  2. Low renal toxicity of lipoplatin compared to cisplatin in animals.

    Science.gov (United States)

    Devarajan, Prasad; Tarabishi, Ridwan; Mishra, Jaya; Ma, Qing; Kourvetaris, Andreas; Vougiouka, Maria; Boulikas, Teni

    2004-01-01

    Cisplatin is one of the most widely used and effective chemotherapeutic agents for the treatment of several human malignancies. Although the effectiveness of cisplatin is high, its toxicities justify the demand for improved formulations of this drug. A liposomal formulation of cisplatin, Lipoplatin, was developed in order to reduce the systemic toxicity of cisplatin. Mice and rats injected with cisplatin developed renal insufficiency with clear evidence of tubular damage, but those injected with the same dose of Lipoplatin were almost completely free of kidney injury. The maximum levels of total platinum in rat kidneys after intraperitoneal bolus injection of cisplatin or Lipoplatin at similar doses were similar, but the steady state accumulation of total platinum in the kidney was 5 times higher for cisplatin compared to Lipoplatin. This is proposed as one mechanism to explain the low renal toxicity of Lipoplatin.

  3. Animal studies of addictive behavior.

    Science.gov (United States)

    Vanderschuren, Louk J M J; Ahmed, Serge H

    2013-04-01

    It is increasingly recognized that studying drug taking in laboratory animals does not equate to studying genuine addiction, characterized by loss of control over drug use. This has inspired recent work aimed at capturing genuine addiction-like behavior in animals. In this work, we summarize empirical evidence for the occurrence of several DSM-IV-like symptoms of addiction in animals after extended drug use. These symptoms include escalation of drug use, neurocognitive deficits, resistance to extinction, increased motivation for drugs, preference for drugs over nondrug rewards, and resistance to punishment. The fact that addiction-like behavior can occur and be studied in animals gives us the exciting opportunity to investigate the neural and genetic background of drug addiction, which we hope will ultimately lead to the development of more effective treatments for this devastating disorder.

  4. Green biosynthesis, characterization, in vitro antidiabetic activity, and investigational acute toxicity studies of some herbal-mediated silver nanoparticles on animal models

    OpenAIRE

    Kalakotla Shanker; Gottumukkala Krishna Mohan; Md Ashwaq Hussain; Naradala Jayarambabu; Poka Lakshmi Pravallika

    2017-01-01

    Diabetes is a metabolic disorder characterized by hyperglycemia, altered carbohydrate, lipid and protein metabolism. In recent studies, Nanoscience and nanotechnology are blazing fields for researchers; for researchers; of late there has been a prodigious excitement in the field of nanopharmacology to study silver nanoparticle (SNP) synthesis using natural products. Biological methods have been used to synthesize SNPs using medicinally active plants having an antidiabetic role, and this made ...

  5. The risk of contamination of food with toxic substances present in animal feed

    NARCIS (Netherlands)

    Kan, C.A.; Meijer, G.A.L.

    2007-01-01

    Toxic substances such as dioxins, mycotoxins, heavy metals, pesticides, veterinary drugs and polycyclic aromatic hydrocarbons are almost ubiquitous in the environment. Thus, they are also present in ingredients for animal feed. Adequate risk management depends on knowledge of absorption, metabolism,

  6. Biomarkers of teratogenesis: suggestions from animal studies.

    Science.gov (United States)

    Giavini, Erminio; Menegola, Elena

    2012-09-01

    Biomarkers of effect are measurable biochemical, physiological or other alterations within an organism that can be recognized as causing an established or potential impairment of embryo-fetal development. They may be identified studying the mechanisms of action of teratogens. Hyperacetylation of histones, oxidative stress, cholesterol and retinoic acid unbalance are some of the identified mechanisms of action of some known teratogens. Nevertheless, their use is not currently applicable in human pregnancy because of the difficulty of the choice of biological material, the time when the material must be obtained, and the invasivity of methods. Furthermore, before using them in human pregnancy studies, biomarkers should be validated in experimental animals and in epidemiologic studies. On the contrary, some biomarkers could be useful in the screening of developmental toxicity of chemicals and drugs, comparing molecules of the same chemical class or with the similar pharmacologic activity, and using adequate in vitro tests, in order to reduce the use of experimental animals.

  7. Assessment of Acute Toxicity of Hexachloroethane in Laboratory Animals

    Science.gov (United States)

    1978-01-09

    camphoraceous odor, readily sublimes without meltinq and is solubl,: in alcohol. benzene, chloroform, ether and oil: insoluble in water. It is used as a solvent...in explosives, as ý camphor suostitute in celluloid, and as a rubber vulcanizing accelerator.’ It is used in veterinary practice as an anthelminthic...moderately toxic orally, produced reversible eye irritation and little or no skin irritation. Although it sublimes at room temperature

  8. The Occurrence and Toxicity of Indospicine to Grazing Animals

    Directory of Open Access Journals (Sweden)

    Mary T. Fletcher

    2015-07-01

    Full Text Available Indospicine is a non-proteinogenic amino acid which occurs in Indigofera species with widespread prevalence in grazing pastures across tropical Africa, Asia, Australia, and the Americas. It accumulates in the tissues of grazing livestock after ingestion of Indigofera. It is a competitive inhibitor of arginase and causes both liver degeneration and abortion. Indospicine hepatoxicity occurs universally across animal species but the degree varies considerably between species, with dogs being particularly sensitive. The magnitude of canine sensitivity is such that ingestion of naturally indospicine-contaminated horse and camel meat has caused secondary poisoning of dogs, raising significant industry concern. Indospicine impacts on the health and production of grazing animals per se has been less widely documented. Livestock grazing Indigofera have a chronic and cumulative exposure to this toxin, with such exposure experimentally shown to induce both hepatotoxicity and embryo-lethal effects in cattle and sheep. In extensive pasture systems, where animals are not closely monitored, the resultant toxicosis may well occur after prolonged exposure but either be undetected, or even if detected not be attributable to a particular cause. Indospicine should be considered as a possible cause of animal poor performance, particularly reduced weight gain or reproductive losses, in pastures where Indigofera are prevalent.

  9. ACUTE DERMAL TOXICITY STUDIES OF TROISTM IN NEWZEALAND WHITE RABBITS

    Directory of Open Access Journals (Sweden)

    Anurag Payasi

    2010-06-01

    Full Text Available The study was performed to assess the acute dermal toxicity of TroisTM in Newzealand white rabbit. Test substance was applied as such to the shaven skin of group of rabbits at the dose of 2000 mg/Kg body weight. Control group of animals were similarly treated but only with base. Following dosing up to 14 days the rabbits were observed for mortality and clinical sign of toxicity. No visible signs of toxicity after treatment were observed on the animals of both control and treated animals up to 14 days. Various haematological and biochemical parameters were evaluated and found to be in the normal limit, which indicates that no sign of toxicity in NewZealand white rabbits after 14 days treatment in respect to control group, proving safety of TroisTM in topical application.

  10. Subchronic toxicity study of GH transgenic carp.

    Science.gov (United States)

    Yong, Ling; Liu, Yu-Mei; Jia, Xu-Dong; Li, Ning; Zhang, Wen-Zhong

    2012-11-01

    A subchronic toxicity study of GH (growth hormone) transgenic carp was carried out with 60 SD rats aged 4 weeks, weight 115∼125 g. Ten male and 10 female rats were allotted into each group. Animals of the three groups (transgenic carp group (GH-TC), parental carp group (PC) and control group) were fed soy- and alfalfa-free diet (SAFD) with 10% GH transgenic carp powder, 10% parental carp powder or 10% common carp powder for 90 consecutive days, respectively. In the end of study, animals were killed by exsanguination via the carotid artery under diethyl ether anesthesia, then weights of heart, liver, kidneys, spleen, thymus, brain, ovaries and uterus/testis were measured. Pathological examination of organs was determined. Endocrine hormones of triiodothyronine (T3), thyroid hormone (T4), follicle-stimulating hormone (FSH), 17β-estradiol (E2), progesterone (P) and testosterone (T) levels were detected by specific ELISA kit. Parameters of blood routine and blood biochemical were measured. The weights of the body and organs of the rats, food intake, blood routine, blood biochemical test and serum hormones showed no significant differences among the GH transgenic carp-treated, parental carp-treated and control groups (P>0.05). Thus, it was concluded that at the dose level of this study, GH transgenic carp showed no subchronic toxicity and endocrine disruption to SD rats.

  11. Consensus report on the future of animal-free systemic toxicity testing

    OpenAIRE

    Leist, Marcel; Hasiwa, Nina; Rovida, Costanza; Daneshian, Mardas; Basketter, David; Kimber, Ian; Clewell, Harvey; Gocht, Tilman; Goldberg, Alan; Busquet, Francois; Rossi, Anna-Maria; Schwarz, Michael; Stephens, Martin; Taalman, Rob; Knudsen, Thomas B.

    2014-01-01

    Since March 2013, animal use for cosmetics testing for the European market has been banned. This requires a renewed view on risk assessment in this field. However, in other fields as well, traditional animal experimentation does not always satisfy requirements in safety testing, as the need for human-relevant information is ever increasing. A general strategy for animal-free test approaches was outlined by the US National Research Council`s vision document for Toxicity Testing in the 21st Cen...

  12. Review of reproductive and developmental toxicity induced by organotins in aquatic organisms and experimental animals

    Energy Technology Data Exchange (ETDEWEB)

    Hirose, A.; Takagi, A.; Nishimura, T.; Kanno, J.; Ema, M. [National Inst. of Health Sciences, Tokyo (Japan)

    2004-09-15

    Widespread use of organotins has caused increasing amounts to be released into the environment. The most important non-pesticidal route of entry of organotins into the environment is through leaching of organotin-stabilized PVC in water, and the use in antifouling agents, resulting in the introduction of organotin into the aquatic environment. Data are available regarding the detection of butyltins and phenyltins in aquatic marine organisms and marine products. Food chain bioamplification of butyltin in oysters, mud crabs, marine mussels, chinook salmons, dolphins, tunas, and sharks and of phenyltin in carps and horseshoe crabs has been reported. These findings indicate that organotins accumulate in the food chain and are bioconcentrated, and that humans can be exposed to organotins via seafood. The levels of organotin compounds in seafood are not considered to be sufficiently high to affect human health. However, Belfroid et al. (2000) noted that more research on residual TBT levels in seafood was needed before a definitive conclusion on possible health risks could be drawn. Although the toxicity of organotins has been extensively reviewed, the reproductive and developmental toxicity of organotins is not well understood. We summarized the data of the studies on reproductive and developmental toxicity of organotins in aquatic organisms and experimental animals.

  13. Variable toxicity of silver nanoparticles to Daphnia magna: effects of algal particles and animal nutrition.

    Science.gov (United States)

    Conine, Andrea L; Frost, Paul C

    2017-01-01

    Aquatic environments vary widely in aspects other than their physicochemical properties that could alter the toxicity of novel contaminants. One factor that could affect chemical toxicity to aquatic consumers is their nutritional environment as it can strongly affect their physiology and life history. Nutrition has the potential to alter an organism's response to the toxin or how the toxin interacts with the consumer through its food. Here we determined how growth and survival responses of Daphnia to an emerging contaminant, silver nanoparticles (AgNPs), are affected by the presence of food and its stoichiometric food quality. We used a series of survival tests, each slightly modified, to determine whether variable toxicity in different nutritional environments resulted from algal sequestration of AgNPs in a nontoxic form or from changes to the nutritional status of the test animals. We found that the presence of algae, of good or poor quality, reduced the toxicity of AgNPs on animal growth and survival. However, the decrease in AgNP toxicity was greater for animals consuming P-rich compared to P-poor food. We found evidence that this effect of food quality was due to greater algal uptake of AgNPs by P-rich than by P-stressed algae. However, we also found animal nutrition, in the absence of algal AgNP binding, could affect toxicity with P-nourished animals surviving slightly better when exposed to AgNPs compared to their P-stressed counterparts. Our results show an important role for algal particles and their P content in determining the toxicity of AgNPs in natural waters primarily due to their binding and uptake abilities and, less so, to their effects on animal nutrition.

  14. [Important toxic and undesirable effects of medicaments in animals from the pharmacists viewpoint].

    Science.gov (United States)

    Siroká, Zuzana

    2012-10-01

    Both veterinary and human drugs belong to the most common sources of poisoning in companion animals. The most problematic are "over the counter" drugs, mainly those from the group of analgesics, which are often given to animals by their owners who are not informed about their toxicity to animals, and those from the group of antiparasitics, which are often administered in an improper dose and to improper animal species. Pharmacists should play an important role in the education of their clients and animal owners in this field. To be able to give qualified advice and thus decrease the possibility of animal poisoning by drugs, they need to obtain sufficient and up-to-date information in this issue. The aim of this overview is to supply pharmacists with the most important knowledge from the area of drug toxicology in small animals.

  15. Freshwater toxicity testing using rehydrated Philodina sp. (Rotifera) as test animals.

    Science.gov (United States)

    Snell, Terry W; Johnston, Rachel K; Matthews, Amelia B

    2017-10-01

    Rotifers have become widely used in aquatic toxicology as a rapid screening test for toxicity. The commercial availability of diapausing embryos (cysts) have facilitated their popularity because test animals can be obtained without having to master the details of culturing. Other rotifer species have life stages capable of surviving desiccation and also could be used in non-culture systems for toxicity assessment. In this article, we describe a system for toxicity testing in freshwater based on rehydrating desiccated bdelloid rotifers in the genus Philodina. These animals can remain in this anhydrobiotic state for more than one year and then rehydrate within hours to provide animals for toxicity tests. We describe three endpoints: a 1.5 h ingestion test, a 24 h mortality test, and a five day reproductive test. The latter test requires feeding and a method using a dried commercial product is explained. Using desiccated rotifers and dried food in toxicity tests make this system especially attractive because of its flexibility and low threshold of biological expertise required to execute the tests. The use of the Philodina toxicity test is illustrated with four metals: copper, lead, mercury and cadmium. Reproduction generally was the most sensitive endpoint, with EC50s of 0.33, 0.44, 0.60, and 0.12 mg/L, respectively. Ingestion was a close second with EC50s of 0.13, 1.64, 0.64, and 6.26 mg/L, respectively. © 2017 Wiley Periodicals, Inc.

  16. Silymarin protects liver against toxic effects of anti-tuberculosis drugs in experimental animals

    Directory of Open Access Journals (Sweden)

    Izzettin Fikret V

    2008-07-01

    Full Text Available Abstract Background The first line anti-tuberculosis drugs isoniazid (INH, rifampicin (RIF and pyrazinamide (PZA continues to be the effective drugs in the treatment of tuberculosis, however, the use of these drugs is associated with toxic reactions in tissues, particularly in the liver, leading to hepatitis. Silymarin, a standard plant extract with strong antioxidant activity obtained from S. marianum, is known to be an effective agent for liver protection and liver regeneration. The aim of this study was to investigate the protective actions of silymarin against hepatotoxicity caused by different combinations of anti-tuberculosis drugs. Methods Male Wistar albino rats weighing 250–300 g were used to form 6 study groups, each group consisting of 10 rats. Animals were treated with intra-peritoneal injection of isoniazid (50 mg/kg and rifampicin (100 mg/kg; and intra-gastric administration of pyrazinamid (350 mg/kg and silymarin (200 mg/kg. Hepatotoxicity was induced by a combination of drugs with INH+RIF and INH+RIF+PZA. Hepatoprotective effect of silymarin was investigated by co-administration of silymarin together with the drugs. Serum biochemical tests for liver functions and histopathological examination of livers were carried out to demonstrate the protection of liver against anti-tuberculosis drugs by silymarin. Results Treatment of rats with INH+RIF or INH+RIF+PZA induced hepatotoxicity as evidenced by biochemical measurements: serum alanine aminotransferase (ALT, aspartate aminotransferase (AST and alkaline phosphatase (ALP activities and the levels of total bilirubin were elevated, and the levels of albumin and total protein were decreased in drugs-treated animals. Histopathological changes were also observed in livers of animals that received drugs. Simultaneous administration of silymarin significantly decreased the biochemical and histological changes induced by the drugs. Conclusion The active components of silymarin had

  17. Effects of amiodarone on the pharmacokinetics and toxicity of digoxin in laboratory animals.

    Science.gov (United States)

    Staneva-Stoytcheva, D; Kristeva, E

    1992-04-01

    Some pharmacokinetic interactions between digoxin and amiodarone were studied in experiments on rabbits. An increase of digoxin serum levels was established in amiodarone-treated rabbits (amiodarone 30 mg/kg s.c. for five days alone or together with digoxin). The calculated elimination half-life (t 1/2) and the area under the curve (AUC) of digoxin were increased and the digoxin clearance was decreased, being most pronounced in animals receiving amiodarone-digoxin combination for five days. There were no changes either in digoxin toxicity in amiodarone-treated guinea pigs or in serum levels of T4, T3 and TTH. The possible mechanisms of digoxin-amiodarone interactions are discussed.

  18. The role of metabolic biomarkers in drug toxicity studies.

    Science.gov (United States)

    Schnackenberg, Laura K; Beger, Richard D

    2008-01-01

    ABSTRACT Metabolic profiling is a technique that can potentially provide more sensitive and specific biomarkers of toxicity than the current clinical measures benefiting preclinical and clinical drug studies. Both nuclear magnetic resonance (NMR) and mass spectrometry (MS) platforms have been used for metabolic profiling studies of drug toxicity. Not only can both techniques provide novel biomarker(s) of toxicity but the combination of both techniques gives a broader range of metabolites evaluated. Changes in metabolic patterns can provide insight into mechanism(s) of toxicity and help to eliminate a potentially toxic new chemical entity earlier in the developmental process. Metabolic profiling offers numerous advantages in toxicological research and screening as sample collection and preparation are relatively simple. Further, sample throughput, reproducibility, and accuracy are high. The area of drug toxicity of therapeutic compounds has already been impacted by metabolic profiling studies and will continue to be impacted as new, more specific biomarker(s) are found. In order for a biomarker or pattern of biomarkers to be accepted, it must be shown that they originate from the target tissue of interest. Metabolic profiling studies are amenable to any biofluid or tissue sample making it possible to link the changes noted in urine for instance as originating from renal injury. Additionally, the ease of sample collection makes it possible to follow a single animal or subject over time in order to determine whether and when the toxicity resolves itself. This review focuses on the advantages of metabolic profiling for drug toxicity studies.

  19. Accumulation and Toxicity of Superparamagnetic Iron Oxide Nanoparticles in Cells and Experimental Animals

    Directory of Open Access Journals (Sweden)

    Greta Jarockyte

    2016-08-01

    Full Text Available The uptake and distribution of negatively charged superparamagnetic iron oxide (Fe3O4 nanoparticles (SPIONs in mouse embryonic fibroblasts NIH3T3, and magnetic resonance imaging (MRI signal influenced by SPIONs injected into experimental animals, were visualized and investigated. Cellular uptake and distribution of the SPIONs in NIH3T3 after staining with Prussian Blue were investigated by a bright-field microscope equipped with digital color camera. SPIONs were localized in vesicles, mostly placed near the nucleus. Toxicity of SPION nanoparticles tested with cell viability assay (XTT was estimated. The viability of NIH3T3 cells remains approximately 95% within 3–24 h of incubation, and only a slight decrease of viability was observed after 48 h of incubation. MRI studies on Wistar rats using a clinical 1.5 T MRI scanner were showing that SPIONs give a negative contrast in the MRI. The dynamic MRI measurements of the SPION clearance from the injection site shows that SPIONs slowly disappear from injection sites and only a low concentration of nanoparticles was completely eliminated within three weeks. No functionalized SPIONs accumulate in cells by endocytic mechanism, none accumulate in the nucleus, and none are toxic at a desirable concentration. Therefore, they could be used as a dual imaging agent: as contrast agents for MRI and for traditional optical biopsy by using Prussian Blue staining.

  20. Pulmonary Toxicity Studies of Lunar Dusts in Rodents

    Science.gov (United States)

    Lam, Chiu-wing; James, John T.

    2009-01-01

    NASA will build an outpost on the lunar surface for long-duration human habitation and research. The surface of the Moon is covered by a layer of fine, reactive dust, and the living quarters in the lunar outpost are expected to be contaminated by lunar dust. Because the toxicity of lunar dust is not known, NASA has tasked its toxicology laboratory to evaluate the risk of exposure to the dust and to establish safe exposure limits for astronauts working in the lunar habitat. Studies of the pulmonary toxicity of a dust are generally done first in rodents by intratracheal/intrapharyngeal instillation. This toxicity screening test is then followed by an inhalation study, which requires much more of the test dust and is labor intensive. Preliminary results obtained by examining lung lavage fluid from dust-treated mice show that lunar dust was somewhat toxic (more toxic than TiO2, but less than quartz dust). More extensive studies are in progress to further examine lung lavage fluid for biomarkers of toxicity and lung tissues for histopathological lesions in rodents exposed to aged and activated (ground) lunar dust samples. In these studies, reference dusts (TiO2 and quartz) of known toxicities and have industrial exposure limits will be studied in parallel so the relative toxicity of lunar dust can be determined. The results from the instillation studies will be useful for choosing exposure concentrations for the animal inhalation study. The animal inhalation exposure will be conducted with lunar dust simulant prior to the study with the lunar dust. The experiment with the simulate will ensure that the study techniques used with actual lunar dust will be successful. The results of instillation and inhalation studies will reveal the toxicological risk of exposures and are essential for setting exposure limits on lunar dust for astronauts living in the lunar habitat.

  1. Senecio brasiliensis and pyrrolizidine alkaloids: toxicity to animals and human health

    Directory of Open Access Journals (Sweden)

    Helenice de Souza Spinosa

    2013-06-01

    Full Text Available Most economic losses in Brazilian livestock production, especially in horses and cattle, are due to poison plants, such as those of the genus Senecio. Senecio brasiliensis Lessing is the main cause of death in cattle in the state of Rio Grande do Sul. The toxicity of this genus is attributed to their content of pyrrolizidine alkaloids, which undergo liver biotransformation creating toxic metabolites, namely pyrroles. These compounds can be transferred to humans through contaminated animal products or by the use of this plant in folk medicine. Thus, the present article is a review of the species S. brasiliensis, its toxic active principles and the mechanism by which pathogenesis occurs. Other plants with the same toxic principles that are harmful to human health are covered as well.

  2. Review of Ammonium Dinitramide Toxicity Studies

    Science.gov (United States)

    2011-01-01

    reproductive toxicant in rats, causing implantation failure in early gestation; follow-on studies implied that ADN is embryotoxic . EPR studies indicated that...mutagenic. 15. SUBJECT TERMS Ammonium dinitramide, ADN, toxicity, reproductive, embryotoxic , genotoxicity 16. SECURITY CLASSIFICATION OF: U 17...reproductive studies, reproduction and fertility, pre-implantation and post-implantation studies, implied that ADN is embryotoxic . A mouse embryo

  3. Toxicity testing: the search for an in vitro alternative to animal testing.

    Science.gov (United States)

    May, J E; Xu, J; Morse, H R; Avent, N D; Donaldson, C

    2009-01-01

    Prior to introduction to the clinic, pharmaceuticals must undergo rigorous toxicity testing to ensure their safety. Traditionally, this has been achieved using in vivo animal models. However, besides ethical reasons, there is a continual drive to reduce the number of animals used for this purpose due to concerns such as the lack of concordance seen between animal models and toxic effects in humans. Adequate testing to ensure any toxic metabolites are detected can be further complicated if the agent is administered in a prodrug form, requiring a source of cytochrome P450 enzymes for metabolism. A number of sources of metabolic enzymes have been utilised in in vitro models, including cell lines, primary human tissue and liver extracts such as S9. This review examines current and new in vitro models for toxicity testing, including a new model developed within the authors' laboratory utilising HepG2 liver spheroids within a co-culture system to examine the effects of chemotherapeutic agents on other cell types.

  4. The putative multidrug resistance protein MRP-7 inhibits methylmercury-associated animal toxicity and dopaminergic neurodegeneration in Caenorhabditis elegans.

    Science.gov (United States)

    VanDuyn, Natalia; Nass, Richard

    2014-03-01

    Parkinson's disease (PD) is the most prevalent neurodegenerative motor disorder worldwide, and results in the progressive loss of dopamine (DA) neurons in the substantia nigra pars compacta. Gene-environment interactions are believed to play a significant role in the vast majority of PD cases, yet the toxicants and the associated genes involved in the neuropathology are largely ill-defined. Recent epidemiological and biochemical evidence suggests that methylmercury (MeHg) may be an environmental toxicant that contributes to the development of PD. Here, we report that a gene coding for the putative multidrug resistance protein MRP-7 in Caenorhabditis elegans modulates whole animal and DA neuron sensitivity to MeHg. In this study, we demonstrate that genetic knockdown of MRP-7 results in a twofold increase in Hg levels and a dramatic increase in stress response proteins associated with the endoplasmic reticulum, golgi apparatus, and mitochondria, as well as an increase in MeHg-associated animal death. Chronic exposure to low concentrations of MeHg induces MRP-7 gene expression, while exposures in MRP-7 genetic knockdown animals results in a loss of DA neuron integrity without affecting whole animal viability. Furthermore, transgenic animals expressing a fluorescent reporter behind the endogenous MRP-7 promoter indicate that the transporter is expressed in DA neurons. These studies show for the first time that a multidrug resistance protein is expressed in DA neurons, and its expression inhibits MeHg-associated DA neuron pathology.

  5. NATURAL PLANT TOXICANT – CYANOGENIC GLYCOSIDE AMYGDALIN: CHARACTERISTIC, METABOLISM AND THE EFFECT ON ANIMAL REPRODUCTION

    OpenAIRE

    Eduard Kolesár; Marek Halenár; Adriana Kolesárová; Peter Massányi

    2015-01-01

    The amount of cyanogenic glycosides, as natural plant toxicants, in plants varies with plant species and environmental effects. Cyanogenic glycoside as an amygdalin was detected in apricot kernels, bitter almonds and peach, plum, pear and apple seeds. Amygdalin itself is non-toxic, but its HCN production decomposed by some enzymes is toxic substance. Target of this review was to describe the characteristic, metabolism and possible effects of amygdalin on reproductive processes. Previous studi...

  6. Anticancer activities against cholangiocarcinoma, toxicity and pharmacological activities of Thai medicinal plants in animal models

    Directory of Open Access Journals (Sweden)

    Plengsuriyakarn Tullayakorn

    2012-03-01

    Full Text Available Abstract Background Chemotherapy of cholangiocarcinoma (CCA, a devastating cancer with increasing worldwide incidence and mortality rates, is largely ineffective. The discovery and development of effective chemotherapeutics is urgently needed. Methods/Design The study aimed at evaluating anticancer activities, toxicity, and pharmacological activities of the curcumin compound (CUR, the crude ethanolic extracts of rhizomes of Zingiber officinale Roscoe (Ginger: ZO and Atractylodes lancea thung. DC (Khod-Kha-Mao: AL, fruits of Piper chaba Hunt. (De-Plee: PC, and Pra-Sa-Prao-Yhai formulation (a mixture of parts of 18 Thai medicinal plants: PPF were investigated in animal models. Anti-cholangiocarcinoma (anti-CCA was assessed using CCA-xenograft nude mouse model. The antihypertensive, analgesic, anti-inflammatory, antipyretic, and anti-ulcer activities and effects on motor coordination were investigated using Rota-rod test, CODA tail-cuff system, writhing and hot plate tests, carrageenan-induced paw edema test, brewer's yeast test, and alcohol-induced gastric ulcer test, respectively. Acute and subacute toxicity tests were performed according to the OECD guideline for testing of chemicals with modification. Results Promising anticancer activity against CCA in nude mouse xenograft model was shown for the ethanolic extract of AL at all oral dose levels (1000, 3000, and 5000 mg/kg body weight as well as the extracts of ZO, PPF, and CUR compound at the highest dose level (5000, 4000, and 5000 mg/kg body weight, respectively. PC produced no significant anti-CCA activity. Results from acute and subacute toxicity tests both in mice and rats indicate safety profiles of all the test materials in a broad range of dose levels. No significant toxicity except stomach irritation and general CNS depressant signs were observed. Investigation of pharmacological activities of the test materials revealed promising anti-inflammatory (ZO, PPF, and AL, analgesic (CUR and

  7. Testing strategies for embryo-fetal toxicity of human pharmaceuticals. Animal models vs. in vitro approaches: a workshop report.

    Science.gov (United States)

    van der Laan, Jan Willem; Chapin, Robert E; Haenen, Bert; Jacobs, Abigail C; Piersma, Aldert

    2012-06-01

    Reproductive toxicity testing is characterized by high animal use. For registration of pharmaceutical compounds, developmental toxicity studies are usually conducted in both rat and rabbits. Efforts have been underway for a long time to design alternatives to animal use. Implementation has lagged, partly because of uncertainties about the applicability domain of the alternatives. The reproductive cycle is complex and not all mechanisms of development can be mimicked in vitro. Therefore, efforts are underway to characterize the available alternative tests with regard to the mechanism of action they include. One alternative test is the mouse embryonic stem cell test (EST), which has been studied since the late 1990s. It is a genuine 3R "alternative" assay as it is essentially animal-free. A meeting was held to review the state-of-the-art of various in vitro models for prediction of developmental toxicity. Although the predictivity of individual assays is improving, a battery of several assays is likely to have even higher predictivity, which is necessary for regulatory acceptance. The workshop concluded that an important first step is a thorough survey of the existing rat and rabbit studies, to fully characterize the frequency of responses and the types of effects seen. At the same time, it is important to continue the optimization of in vitro assays. As more experience accumulates, the optimal conditions, assay structure, and applicability of the alternative assays are expected to emerge. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Malaria in cynomolgus monkeys used in toxicity studies in Japan.

    Science.gov (United States)

    Ohta, Etsuko; Nagayama, Yuko; Koyama, Naoki; Kakiuchi, Dai; Hosokawa, Satoru

    2016-01-01

    Plasmodium spp. protozoa cause malaria and are known to infect humans and a variety of animal species including macaque monkeys. Here we report both our experience with malaria recrudescence in cynomolgus monkeys (Macaca fascicularis) in a toxicity study and the results of a survey on Plasmodium infection in cynomolgus monkeys imported to Japan for laboratory use. A cynomolgus monkey from the toxicity study presented with severe anemia and Plasmodium protozoa in erythrocytes on a thin blood smear and was subsequently diagnosed with symptomatic malaria. In this animal, congestion and accumulation of hemozoin (malaria pigment) in macrophages were noted in the enlarged and darkly discolored spleen. As a follow-up for the experience, spleen sections from 800 cynomolgus monkeys in toxicity studies conducted between 2003 and 2013 were retrospectively examined for hemozoin deposition as a marker of Plasmodium infection. The origin of the animals included Cambodia, China, Indonesia, and Vietnam. Hemozoin deposition was confirmed in 44% of all examined monkeys. Monkeys from Indonesia showed the highest incidence of hemozoin deposition (approx. 80%). A high prevalence of Plasmodium infection in laboratory monkeys was also confirmed with polymerase chain reaction (PCR) by using Plasmodium genus-specific primers. Although Japan is not a country with endemic malaria, it is important to be aware of the prevalence and potential impact of background infection with Plasmodium spp. and recrudescence of symptomatic malaria in imported laboratory monkeys on pharmaceutical toxicity studies.

  9. Consensus report on the future of animal-free systemic toxicity testing.

    Science.gov (United States)

    Leist, Marcel; Hasiwa, Nina; Rovida, Costanza; Daneshian, Mardas; Basketter, David; Kimber, Ian; Clewell, Harvey; Gocht, Tilman; Goldberg, Alan; Busquet, Francois; Rossi, Anna-Maria; Schwarz, Michael; Stephens, Martin; Taalman, Rob; Knudsen, Thomas B; McKim, James; Harris, Georgina; Pamies, David; Hartung, Thomas

    2014-01-01

    Since March 2013, animal use for cosmetics testing for the European market has been banned. This requires a renewed view on risk assessment in this field. However, in other fields as well, traditional animal experimentation does not always satisfy requirements in safety testing, as the need for human-relevant information is ever increasing. A general strategy for animal-free test approaches was outlined by the US National Research Council`s vision document for Toxicity Testing in the 21st Century in 2007. It is now possible to provide a more defined roadmap on how to implement this vision for the four principal areas of systemic toxicity evaluation: repeat dose organ toxicity, carcinogenicity, reproductive toxicity and allergy induction (skin sensitization), as well as for the evaluation of toxicant metabolism (toxicokinetics) (Fig. 1). CAAT-Europe assembled experts from Europe, America and Asia to design a scientific roadmap for future risk assessment approaches and the outcome was then further discussed and refined in two consensus meetings with over 200 stakeholders. The key recommendations include: focusing on improving existing methods rather than favoring de novo design; combining hazard testing with toxicokinetics predictions; developing integrated test strategies; incorporating new high content endpoints to classical assays; evolving test validation procedures; promoting collaboration and data-sharing of different industrial sectors; integrating new disciplines, such as systems biology and high throughput screening; and involving regulators early on in the test development process. A focus on data quality, combined with increased attention to the scientific background of a test method, will be important drivers. Information from each test system should be mapped along adverse outcome pathways. Finally, quantitative information on all factors and key events will be fed into systems biology models that allow a probabilistic risk assessment with flexible

  10. [Health effects of solar cell component material. Toxicity of indium compounds to laboratory animals determined by intratracheal instillations].

    Science.gov (United States)

    Tanaka, Akiyo; Hirata, Miyuki

    2013-01-01

    Owing to the increasing interest being paid to the issue of the global environment, the production of solar cells has increased rapidly in recent years. Copper indium gallium diselenide (CIGS) is a new efficient thin film used in some types of solar cell. Indium is a constitutive element of CIGS thin-film solar cells. It was thought that indium compounds were not harmful until the beginning of the 1990s because there was little information regarding the adverse health effects on humans or animals arising from exposure to indium compounds. After the mid-1990s, data became available indicating that indium compounds can be toxic to animals. In animal studies, it has been clearly demonstrated that indium compounds cause pulmonary toxicity and that the dissolution of indium compounds in the lungs is considerably slow, as shown by repeated intratracheal instillations in experimental animals. Thus, it is necessary to pay much greater attention to human exposure to indium compounds, and precautions against possible exposure to indium compounds are paramount with regard to health management.

  11. Evaluation of 90 day repeated dose oral toxicity and reproductive/developmental toxicity of 3'-hydroxypterostilbene in experimental animals.

    Science.gov (United States)

    Majeed, Muhammed; Bani, Sarang; Natarajan, Sankaran; Pandey, Anjali; S, Naveed

    2017-01-01

    3'-Hydroxypterostilbene (3'-HPT) is one of the active constituents of Sphaerophysa salsula and Pterocarpus marsupium. Despite many proposed therapeutic applications, the safety profile of 3'-HPT has not been established. The present work investigated 90 day repeated oral dose and reproductive (developmental) toxicity of 3'-HPT as a test substance in rats as per OECD guidelines. 90 day toxicity was conducted in sixty Sprague Dawley rats of each sex (120 rats), grouped into six dosage groups of 0 (control), 0 (control recovery), 20 (low dose), 80 (mid dose), 200 (high dose) and 200 (high dose recovery) mg/kg bwt/day (body weight/day) respectively. For the reproductive toxicity study forty Wistar rats of each sex (80 rats) divided into four dosage groups received 0 (vehicle control), 20 (low dose), 100 (mid dose) and 200 (high dose) mg/kg bwt/day of 3'-HPT respectively for a period of two weeks while pre-mating, mating, on the day before sacrifice, in females during pregnancy and four days of lactation period. Results showed no significant differences in body weight, food intake, absolute organ weight, haematology, with no adverse effects (toxicity) on biochemical values nor any abnormal clinical signs or behavioural changes were observed in any of the control/treatment groups, including reproductive and developmental parameters, gross and histopathological changes. In conclusion, the results suggested a No-Observed-Adverse-Effect-Level (NOAEL) of 200 mg/kg bwt/day in rats after oral administration, implying 3'-HPT did not exhibit any toxicity under the study conditions employed.

  12. Examining the antimicrobial activity and toxicity to animal cells of different types of CO-releasing molecules.

    Science.gov (United States)

    Nobre, Lígia S; Jeremias, Hélia; Romão, Carlos C; Saraiva, Lígia M

    2016-01-28

    Transition metal carbonyl complexes used as CO-releasing molecules (CORMs) for biological and therapeutic applications may exhibit interesting antimicrobial activity. However, understanding the chemical traits and mechanisms of action that rule this activity is required to establish a rationale for the development of CORMs into useful antibiotics. In this work the bactericidal activity, the toxicity to eukaryotic cells, and the ability of CORMs to deliver CO to bacterial and eukaryotic cells were analysed for a set of seven CORMs that differ in the transition metal, ancillary ligands and the CO release profile. Most of these CORMs exhibited bactericidal properties that decrease in the following order: CORM-2 > CORM-3 > ALF062 > ALF850 > ALF186 > ALF153 > [Fe(SBPy3)(CO)](BF4)2. A similar yet not entirely coincident decreasing order was found for their induction of intracellular reactive oxygen species (ROS) in E. coli. In contrast, studies in model animal cells showed that for any given CORM, the level of intracellular ROS generated was negligible when compared with that measured inside bacteria. Importantly, these CORMs were in general not toxic to eukaryotic cells, namely murine macrophages, kidney LLC-PK1 epithelial cells, and liver cell line HepG2. CORM-2 and CORM-3 delivered CO to the intracellular space of both E. coli and the two types of tested eukaryotic cells, yet toxicity was only elicited in the case of E. coli. CO delivered by ALF186 into the intercellular space did not enter E. coli cells and the compound was not toxic to either bacteria or to eukaryotic cells. The Fe(ii) carbonyl complex [Fe(SBPy3)(CO)](2+) had the reverse, undesirable toxicity profile, being unexpectedly toxic to eukaryotic cells and non-toxic to E. coli. ALF153, the most stable complex in the whole set, was essentially devoid of toxicity or ROS induction ability in all cells. These results suggest that CORMs have a relevant therapeutic potential as antimicrobial drugs since (i) they

  13. International Conference on Harmonisation; guidance on the duration of chronic toxicity testing in animals (rodent and nonrodent toxicity testing); availability. Notice. Food and Drug Administration, HHS.

    Science.gov (United States)

    1999-06-25

    The Food and Drug Administration (FDA) is publishing a guidance entitled "S4A Duration of Chronic Toxicity Testing in Animals (Rodent and Nonrodent Toxicity Testing)." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and is intended to provide guidance on the duration of chronic toxicity testing in rodents and nonrodents as part of the safety evaluation of a drug product. FDA is also noting circumstances in which it may accept durations of chronic toxicity testing in nonrodents that differ from the duration generally recommended by ICH.

  14. Arsenic toxicity in mammals and aquatic animals: a comparative biochemical approach.

    Science.gov (United States)

    Ventura-Lima, Juliane; Bogo, Maurício Reis; Monserrat, José M

    2011-03-01

    Arsenic (As) is a widespread pollutant in the world and its toxicity is related to its chemical form, with inorganic forms being considered more toxic than the organic form, and huge differences in effects and processes of metabolism. This paper reviews the potential biochemical mechanisms of uptake of arsenic by aquaporins, capacity for metabolism and cellular efflux of As. It is known that As can affect signaling pathways since it can activate proteins such as ERK2, p38 and JNK, as shown in mammals. A comparison between phosphorylation sites of these proteins is presented in order to determine whether the same effect triggered by As in mammals might be observed in aquatic animals. The toxicity resulting from As exposure is considered to be linked to an imbalance between pro-oxidant and antioxidant homeostasis that results in oxidative stress. So, present review analyzes examples of oxidative stress generation by arsenic. Biotransformation of As is a process where firstly the arsenate is converted into arsenite and then transformed into mono-, di-, and trimethylated products. In the methylation process, the role of the omega isoform of glutathione-S-transferase (GST) is discussed. In addition, a phylogenetic tree was constructed for aquaporin proteins of different species, including aquatic animals, taking into account their importance in trivalent arsenic uptake.

  15. Trichothecene toxicity in eukaryotes: cellular and molecular mechanisms in plants and animals.

    Science.gov (United States)

    Arunachalam, Chanemougasoundharam; Doohan, Fiona M

    2013-02-27

    Trichothecenes are sesquiterpenoid mycotoxins commonly found as contaminants in cereal grains and are a major health and food safety concern due to their toxicity to humans and farm animals. Trichothecenes are predominantly produced by the phytopathogenic Fusarium fungus, and in plants they act as a virulence factor aiding the spread of the fungus during disease development. Known for their inhibitory effect on eukaryotic protein synthesis, trichothecenes also induce oxidative stress, DNA damage and cell cycle arrest and affect cell membrane integrity and function in eukaryotic cells. In animals, trichothecenes can be either immunostimulatory or immunosuppressive and induce apoptosis via mitochondria-mediated or -independent pathway. In plants, trichothecenes induce programmed cell death via production of reactive oxygen species. Recent advances in molecular techniques have led to the elucidation of signal transduction pathways that manifest trichothecene toxicity in eukaryotes. In animals, trichothecenes induce mitogen-activated protein kinase (MAPK) signalling cascades via ribotoxic stress response and/or endoplasmic reticulum stress response. The upstream signalling events that lead to the activation trichothecene-induced ribotoxic stress response are discussed. In plants, trichothecenes exhibit elicitor-like activity leading to the inductions MAPKs and genes involved in oxidative stress, cell death and plant defence response. Trichothecenes might also modulate hormone-mediated defence signalling and abiotic stress signalling in plants.

  16. FUNCTIONAL-ASPECTS OF DEVELOPMENTAL TOXICITY OF POLYHALOGENATED AROMATIC-HYDROCARBONS IN EXPERIMENTAL-ANIMALS AND HUMAN INFANTS

    NARCIS (Netherlands)

    BROUWER, A; AHLBORG, UG; VANDENBERG, M; BIRNBAUM, LS; BOERSMA, ER; BOSVELD, B; DENISON, MS; GRAY, LE; HAGMAR, L; HOLENE, E; HUISMAN, M; JACOBSON, SW; JACOBSON, JL; KOOPMANESSEBOOM, C; KOPPE, JG; KULIG, BM; MORSE, DC; MUCKLE, G; PETERSON, RE; SAUER, PJJ; SEEGAL, RF; SMITSVANPROOIJE, AE; TOUWEN, BCL; WEISGLASKUPERUS, N; WINNEKE, G

    1995-01-01

    A scientific evaluation was made of functional aspects of developmental toxicity of polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in experimental animals and in human infants. Persistent neurobehavioral, reproductive and endocri

  17. Acute silver toxicity in aquatic animals is a function of sodium uptake rate

    DEFF Research Database (Denmark)

    Bianchini, A.; Grosell, Martin Hautopp; Gregory, S.

    2002-01-01

    -specific surface area of the gills depends on animal body mass; and (iv) the gill surface is also the major site of Na+ loss by diffusion, we hypothesized that whole body Na+ uptake rate (i.e., turnover rate) and secondarily body mass would be good predictors of acute silver toxicity. Results obtained from...... toxicological (LC50 of AgNO3) and physiological (22Na uptake rate) tests performed on juvenile fish (rainbow trout, Oncorhynchus mykiss), early juvenile and adult crayfish (Cambarus diogenes diogenes), and neonate and adult daphnids (Daphnia magna) in moderately hard water of constant quality support the above...

  18. Preliminary acute toxicity study on imidacloprid in Swiss albino mice

    Directory of Open Access Journals (Sweden)

    Preeti Bagri

    2013-12-01

    Full Text Available Aim: To ascertain the maximum tolerated dose (MTD and to investigate the acute oral toxic effects of imidacloprid towards Swiss albino male mice.Materials and Methods: The MTD of imidacloprid was determined in pilot dose range finding study following the standard method. Animals were observed for toxic signs and symptoms after oral administration of MTD of imidacloprid in single dose. The body weights of animals were recorded on alternate day. Animals were sacrificed on 14th day and changes in hematological parameters (Hb, TEC, TLC and DLC and morphometric measurements (length, breadth, thickness and weight of various body organs (heart, liver, spleen, kidney, testis and epididymis were examined. The student's t-test was applied to statistically analyze the results.Results: The MTD of imidacloprid was determined to be 110 mg/kg body weight. The sign and symptoms of acute toxicity were ataxia, rigidity and fasciculation of muscles, protrusion of eye ball and tremors of head. Imidacloprid treatment resulted in decreased body weight gain as compared to the control group. The changes in hematological parameters were not significant between imidacloprid treated and control groups. Also the values of relative organ weights and morphometric measurements of various body organs did not differ significantly between the control and imidacloprid treated animals.Conclusions: MTD of imidacloprid in Swiss albino male mice through oral route was determined for the first time. Study revealed a non-toxic effect of imidacloprid on body weight, relative organs weight, hematological parameters and morphometric measurements of various body organs in mice.

  19. Methods of acute biological assays in guinea-pigs for the study of toxicity and innocuity of drugs and chemicals

    OpenAIRE

    2010-01-01

    In this study, 602 samples were tested by the following assays performed at the animal facilities (Cedeme) of the Federal University of São Paulo (UNIFESP): 385 for dermal irritability, 90 for ocular irritability (discontinued in 1995), 31 for systemic toxicity by injection, 26 for oral acute toxicity, 15 for toxicity by intracutaneous injection, 15 for skin sensitization, 15 for toxicity of serum and vaccines for human use, 14 for toxicity by intramuscular implantation, 7 for pyrogens, 2 for...

  20. Body-on-a-chip systems for animal-free toxicity testing.

    Science.gov (United States)

    Mahler, Gretchen J; Esch, Mandy B; Stokol, Tracy; Hickman, James J; Shuler, Michael L

    2016-10-01

    Body-on-a-chip systems replicate the size relationships of organs, blood distribution and blood flow, in accordance with human physiology. When operated with tissues derived from human cell sources, these systems are capable of simulating human metabolism, including the conversion of a prodrug to its effective metabolite, as well as its subsequent therapeutic actions and toxic side-effects. The system also permits the measurement of human tissue electrical and mechanical reactions, which provide a measure of functional response. Since these devices can be operated with human tissue samples or with in vitro tissues derived from induced pluripotent stem cells (iPS), they can play a significant role in determining the success of new pharmaceuticals, without resorting to the use of animals. By providing a platform for testing in the context of human metabolism, as opposed to animal models, the systems have the potential to eliminate the use of animals in preclinical trials. This article will review progress made and work achieved as a direct result of the 2015 Lush Science Prize in support of animal-free testing. 2016 FRAME.

  1. Subchronic (13-week) toxicity and prenatal developmental toxicity studies of dietary astaxanthin in rats.

    Science.gov (United States)

    Vega, Katherine; Edwards, James; Beilstein, Paul

    2015-12-01

    Two studies examined the effects of dietary astaxanthin on Hanlbm Wistar (SPF) rats. Male and female rats receiving astaxanthin concentrations up to 1.52% of the feed for 13 weeks showed no evidence of toxicity; no effects were noted in the offspring of female rats exposed to astaxanthin at up to 1.39% of the feed during the period of organogenesis (GD 7-16). Discoloration of the feces and yellow pigmentation of adipose tissue was seen in the 13-week study, an intrinsic property of the substance, and not a sign of toxicity. Differences between the control and astaxanthin groups, some of which reached statistical significance, were generally sporadic (i.e., transient and/or not related to astaxanthin concentration) and not considered of biological or toxicological significance. Blood cholesterol levels, for example, were greater in animals receiving astaxanthin for 13 weeks, but remained within the normal range. The highest dietary concentration of astaxanthin in each of the studies is proposed as a no-observable-adverse-effect level (NOAEL). Specifically, 1.52% for the 13-week study, corresponding to a mean intake of 1033 mg/kg bw/day (range: 880-1240 mg/kg bw/day), and 1.39% for the developmental toxicity study, corresponding to a mean intake of approximately 830 mg/kg bw/day (range: 457-957 mg/kg bw/day).

  2. 栀子对闹羊花急性中毒解毒效应的动物实验研究%Animal Experimental Study of Detoxication Effect in Fructus Gardeniae to Acute Toxicity of Flos Rhododendri Mollis

    Institute of Scientific and Technical Information of China (English)

    姚敏; 代文月; 金柳燕; 何丽美; 囤荣梁; 高维琴

    2011-01-01

    目的 研究闹羊花的急性中毒现象以及栀子对闹羊花的急性解毒效应.方法 闹羊花的急性中毒实验,小鼠分别灌胃生理盐水和不同质量浓度的闹羊花水煎剂并对其行为学变化进行观察;栀子对闹羊花的急性解毒效应实验,小鼠分别灌胃生理盐水、闹羊花、栀子、闹羊花与不同质量浓度栀子的水煎剂,观察其形态学变化,检测心脏匀浆中的SOD活性、MDA含量与血清中CK含量.结果 闹羊花的急性毒性试验中,闹羊花的毒性表现为小鼠星醉酒状,翻正反射消失;小剂量时翻正反射能恢复,大剂量时小鼠死亡,且其中毒率、翻正反射消失率和死亡率随着剂量的增大而增高,而其翻正反射恢复率与剂量呈反比.栀子对闹羊花的解毒效应实验中,闹羊花组与生理盐水组和闹羊花+高剂量栀子组相比,CK含最明显偏高,且SOD活性较该两组偏低,MDA含量较生理盐水组和闹羊花+各剂量组偏高,但较栀子组明显偏低,并且闹羊花与栀子配伍小鼠情况更稳定.结论 闹羊花对小鼠具有神经系统和心血管系统毒性;栀子对闹羊花具有解毒效应,作用与两者配伍能减轻心脏的氧化损伤有关.%Objective: To study the acute toxicity of Flos Rhododendri Mollis and the detoxification of Fructus Gardeniae to it. Methods: Mice were administered intragastrically daily with the saline and several dosages of Flos Rhododendri Mollis. The change of behavior in these mice were observed. Meanwhile, mice were administered intragastrically with the Flos Rhododendri Mollis decoction, the Fructus Gardeniae decoction, and the Flos Rhododendri Mollis with different concentrations of Fructus Gardeniae. The SOD activity, the MDA content in heart and the serum CK were measured. Results: In the acute toxicity experiment of Flos Rhododendri Mollis, the toxicity was drunkness. The righting reflex was disappeared. When administration of low dosage, the righting

  3. Epigenetic Case Studies in Agricultural Animals

    Science.gov (United States)

    In many biological processes, the regulation of gene expression involves epigenetic mechanisms. An altered pattern of epigenetic modification is central to many animal diseases. Using animal disease models, we have studied one of the major epigenetic components: DNA methylation. We characterized the...

  4. A Comprehensive Study of Underground Animals Habitat

    Science.gov (United States)

    Klokov, A. V.; Zapasnoy, A. S.; Mironchev, A. S.; Yakubov, V. P.; Shipilova, S. S.

    2016-01-01

    This paper describes a method of studying the natural habitats of underground animals by the example of zokor. The purpose of the research is to find habitation of animals using unmanned aircraft and investigate networks of tunnels and burrows with ground penetrating radar "OKO-2". Geolocation data were processed by techniques developed by the authors.

  5. NATURAL PLANT TOXICANT – CYANOGENIC GLYCOSIDE AMYGDALIN: CHARACTERISTIC, METABOLISM AND THE EFFECT ON ANIMAL REPRODUCTION

    Directory of Open Access Journals (Sweden)

    Eduard Kolesár

    2015-02-01

    Full Text Available The amount of cyanogenic glycosides, as natural plant toxicants, in plants varies with plant species and environmental effects. Cyanogenic glycoside as an amygdalin was detected in apricot kernels, bitter almonds and peach, plum, pear and apple seeds. Amygdalin itself is non-toxic, but its HCN production decomposed by some enzymes is toxic substance. Target of this review was to describe the characteristic, metabolism and possible effects of amygdalin on reproductive processes. Previous studies describe the effects of natural compound amygdalin on female and male reproductive systems focused on process of steroidogenesis, spermatozoa motility and morphological abnormalities of spermatozoa. In accordance to the previous studies on amygdalin its benefit is controversial.

  6. Two-generation reproduction toxicity study in rats with methoxychlor.

    Science.gov (United States)

    Aoyama, Hiroaki; Hojo, Hitoshi; Takahashi, Ken L; Shimizu-Endo, Naoko; Araki, Masayuki; Takeuchi-Kashimoto, Yukiko; Saka, Machiko; Teramoto, Shoji

    2012-03-01

    A two-generation reproduction toxicity study was conducted in rats with a reference estrogenic pesticide, methoxychlor, to validate the sensitivity and competency of current guidelines recommended by the United States Environmental Protection Agency; Japanese Ministry of Agriculture, Forestry and Fisheries; and Organisation for Economic Co-operation and Development for predicting reproductive toxicity of the test compound based on estrogenic endocrine disrupting effects. Both sexes of SD rats were exposed to methoxychlor in the diet at concentrations of 0, 10, 500 and 1500 ppm for two successive generations. The present study has successfully detected estrogenic activities and reproductive toxicities of methoxychlor, as well as its systemic toxicity. Body weights, body weight gains and food consumption of both sexes of animals were suppressed significantly in the 500 and 1500 ppm groups. Typical reproductive toxicities observed in females of these groups included, but were not limited to, prolonged estrous cycle, reduced fertility, decreased numbers of implantation sites and newborns, decreased ovary weights and/or increased incidences of cystic ovary. Uterine weights of weanlings increased significantly in these groups, suggesting that the sensitivity of this parameter for predicting estrogenic ability of the test compound is comparable to that of the uterotrophic assay. Reproductive toxicities of methoxychlor seemed less potent in males than in females. Methoxychlor delayed preputial separation and significantly reduced sperm counts and reproductive organ weights of males of the 500 and/or 1500 ppm groups; however, most males that failed to impregnate females in the same group showed normal fertility when they were re-mated with untreated females. Neither systemic nor reproductive toxicities appeared in the 10 ppm group.

  7. A new mechanism of macrophyte mitigation: how submerged plants reduce malathion's acute toxicity to aquatic animals.

    Science.gov (United States)

    Brogan, William R; Relyea, Rick A

    2014-08-01

    A growing body of evidence suggests that aquatic plants can mitigate the toxicity of insecticides to sensitive aquatic animals. The current paradigm is that this ability is driven primarily by insecticide sorption to plant tissues, especially for hydrophobic compounds. However, recent work shows that submerged plants can strongly mitigate the toxicity of the relatively hydrophilic insecticide malathion, despite the fact that this compound exhibits a slow sorption rate to plants. To examine this disparity, we tested the hypothesis that the mitigating effect of submerged plants on malathion's toxicity is driven primarily by the increased water pH from plant photosynthesis causing the hydrolysis of malathion, rather than by sorption. To do this, we compared zooplankton (Daphnia magna) survival across five environmentally relevant malathion concentrations (0, 1, 4, 6, or 36 μg L(-1)) in test containers where we chemically manipulated water pH in the absence of plants or added the submerged plant (Elodea canadensis) but manipulated plant photosynthetic activity via shading or no shading. We discovered that malathion was equally lethal to Daphnia at all concentrations tested when photosynthetically inactive (i.e. shaded) plants were present (pH at time of dosing=7.8) or when pH was chemically decreased (pH=7.7). In contrast, when photosynthetically active (i.e. unshaded) plants were present (pH=9.8) or when pH was chemically increased (pH=9.5), the effects of 4 and 6 μg L(-1) of malathion on Daphnia were mitigated strongly and to an equal degree. These results demonstrate that the mitigating effect of submerged plants on malathion's toxicity can be explained entirely by a mechanism of photosynthesizing plants causing an increase in water pH, resulting in rapid malathion hydrolysis. Our findings suggest that current ecotoxicological models and phytoremediation strategies may be overlooking a critical mechanism for mitigating pesticides.

  8. Toxicity Studies on "840 Biologic Pesticide"

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    [Objective] "840 Biologic Pesticide" is a very effective biologic pesticide. It consists of Abamectin and celastrus angulatus. Toxicity study was aimed to provide scientific toxicological basis. [Methods] The acute toxicity test,Ames test,micronucleus test and testicle chromosome aberration test were done. [Results] The acute toxicity of single dose of "840 Biologic Pesticide" showed that acute oral LD50 for female and male rats are 4 300 and 4 280 mg/kg,and for female and male mice are 2 330 and 5 110 mg/kg,respectively. The dermal LD50 was >2 000 mg/kg for female and male rats. The mutagenesis studies indicated that Ames test,micronucleus test and testicle chromosome aberration test were negative. [Conclusion] Tested pesticidc belongs to low toticity grade.

  9. Using the nematode Caenorhabditis elegans as a model animal for assessing the toxicity induced by microcystin-LR

    Institute of Scientific and Technical Information of China (English)

    LI Yunhui; WANG Yang; YIN Lihong; PU Yuepu; WANG Dayong

    2009-01-01

    Among more than 75 variants of microcystin (MC), microcystin-LR (MC-LR) is one of the most common toxins. In this study, the feasibility of using Caenorhabditis elegans to evaluate MC-LR toxicity was studied. C. elegans was treated with MC-LR at different concentrations ranging from 0.1 to 80 μg/L. The results showed that MC-LR could reduce lifespan, delay development, lengthen generation times, decrease brood sizes, suppress locomotion behaviors, and decreases hsp-16-2-gfp expression. The endpoints of generation time, brood size, and percentage of the population expressing hsp16-2-gfp were very sensitive to 1.0 μg/L of MC-LR, and would be more useful for the evaluation of MC-LR toxicity. Furthermore, the tissue-specific hsp16-2-gfp expressions were investigated in MC-LR-exposed animals, and the nervous system and intestine were primarily effected by MC-LR. Therefore, the generation time, brood size, and hsp16-2-gfp expression in C. elegans can be explored to serve as valuable endpoints for evaluating the potential toxicity from MC-LR exposure.

  10. Satellite animal tracking feasibility studies

    Science.gov (United States)

    Buechner, H. K.

    1975-01-01

    A study was initiated in Tsavo National Park to determine movements and home ranges of individual elephants and their relations to overall distribution patterns and environmental factors such as rainfall. Methods used were radio tracking and observations of visually identifiable individuals. Aerial counts provided data on overall distribution. Two bulls and two cows were radio-tagged in Tsavo West and two bulls and four cows in Tsavo East, providing home range and movement data. The movements of individuals were useful in interpreting relatively major shifts in elephant distribution. Results point to the following preliminary conclusions: (1) elephants in the Tsavo area undertook long distance movements in fairly direct response to localized rainfall; (2) a subdivision of the overall population into locally distinct units may exist during the dry season but did not occur after significant rainfall; and (3) food appears to be the primary factor governing movements and distribution of elephants in the area.

  11. Animal models for the study of tendinopathy

    Science.gov (United States)

    Warden, S J

    2007-01-01

    Tendinopathy is a common and significant clinical problem characterised by activity‐related pain, focal tendon tenderness and intratendinous imaging changes. Recent histopathological studies have indicated the underlying pathology to be one of tendinosis (degeneration) as opposed to tendinitis (inflammation). Relatively little is known about tendinosis and its pathogenesis. Contributing to this is an absence of validated animal models of the pathology. Animal models of tendinosis represent potential efficient and effective means of furthering our understanding of human tendinopathy and its underlying pathology. By selecting an appropriate species and introducing known risk factors for tendinopathy in humans, it is possible to develop tendon changes in animal models that are consistent with the human condition. This paper overviews the role of animal models in tendinopathy research by discussing the benefits and development of animal models of tendinosis, highlighting potential outcome measures that may be used in animal tendon research, and reviewing current animal models of tendinosis. It is hoped that with further development of animal models of tendinosis, new strategies for the prevention and treatment of tendinopathy in humans will be generated. PMID:17127722

  12. Animal models for the study of tendinopathy.

    Science.gov (United States)

    Warden, S J

    2007-04-01

    Tendinopathy is a common and significant clinical problem characterised by activity-related pain, focal tendon tenderness and intratendinous imaging changes. Recent histopathological studies have indicated the underlying pathology to be one of tendinosis (degeneration) as opposed to tendinitis (inflammation). Relatively little is known about tendinosis and its pathogenesis. Contributing to this is an absence of validated animal models of the pathology. Animal models of tendinosis represent potential efficient and effective means of furthering our understanding of human tendinopathy and its underlying pathology. By selecting an appropriate species and introducing known risk factors for tendinopathy in humans, it is possible to develop tendon changes in animal models that are consistent with the human condition. This paper overviews the role of animal models in tendinopathy research by discussing the benefits and development of animal models of tendinosis, highlighting potential outcome measures that may be used in animal tendon research, and reviewing current animal models of tendinosis. It is hoped that with further development of animal models of tendinosis, new strategies for the prevention and treatment of tendinopathy in humans will be generated.

  13. CDP-choline: acute toxicity study.

    Science.gov (United States)

    Grau, T; Romero, A; Sacristán, A; Ortiz, J A

    1983-01-01

    The acute toxicity of a single dose of cytidine diphosphate choline (CDP-choline, citicoline, Somazina) by different administration routes in mice and rats has been studied. LD50 values were determined according to the cumulative method by Reed-Muench for mortality rate, and Pizzi's method for calculation of standard error.

  14. Subacute (90 Days) Oral Toxicity Studies of Kombucha Tea

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Kombucha tea (KT) is a popular health beverage and is used as an alternative therapy. KT is prepared by placing the kombucha culture in solution of tea and sugar and allowing to ferment. The inoculum is a fungus consisting of symbiotic colony of yeast and bacteria. KT is consumed in several countries and is believed to have prophylactic and therapeutic benefits in a wide variety of ailments, viz., intestinal disorders, arthritis, ageing and stimulation of immunological system. Though KT is used in several parts of the world its beneficial effects and adverse effects have not been scientifically evaluated. Since there are no animal toxicological data on KT, subacute oral toxicity study was carried out. Five groups of rats were maintained: (a) control group given tap water orally, (b) KT given 2 ml/kg orally, (c) plain tea (PT) given 2 ml/kg orally, (d) KT given in drinking water, 1% (v/v) and (e) PT given in drinking water, 1% (v/v). The rats were given this treatment daily for a period of 90 days. Weekly records of weight, feed intake, water intake and general behaviour were monitored. There was no significant difference in the growth of the animals as evidenced by the progressive body weight change. The organ to body weight ratio and histological evaluation did not show any toxic signs. The haematological and biochemical variables were within the clinical limits. The study indicates that rats fed KT for 90 days showed no toxic effects.

  15. Reproducibility of toxicity test data as a function of mouse strain, animal lot, and operator. [for bisphenol A polycarbonate

    Science.gov (United States)

    Hilado, C. J.; Furst, A.

    1978-01-01

    The toxicity screening test method developed at the University of San Francisco was evaluated for reproducibility. The variables addressed were strain of mouse, lot of animals, and operator. There was a significant difference in response between Swiss Webster mice and ICR mice, with the latter exhibiting greater resistance. These two strains of mice are not interchangeable in this procedure. Variation between individual animals was significant and unavoidable. In view of this variation, between-lot and between-operator variations appear to have no practical significance. The significant variation between individual animals stresses the need for average values based on at least four animals, and preferably values based on at least two experiments and eight animals. Efforts to compare materials should be based on the evaluation of relatively simple responses using substantial numbers of animals, rather than on elaborate evaluation of single animals

  16. Developmental toxicity study of pentachlorophenol in the rabbit.

    Science.gov (United States)

    Bernard, B K; Ranpuria, A K; Hoberman, A M

    2001-01-01

    The potential for developmental toxicity of pentachlorophenol (penta) was studied in New Zealand white rabbits at doses of 0 (corn oil), 7.5, 15, and 30 mg/kg/day administered by gavage on days 6 to 18 of gestation. The rabbits were sacrificed on day 29 of presumed gestation and necropsied. Measurements included number of corpora lutea, pregnancy, number and distribution of implantations, early and late resorptions, live and dead fetuses, fetal weight, gender, and gross external, soft tissue, and skeletal alterations. The mid and high doses reduced maternal body weight gain; the high dose caused transient weight loss and reduced feed consumption. There were no effects on embryofetal development at any of the doses evaluated. Based on these data, the maternal no-observable-adverse-effect level (NOAEL) is 7.5 mg/kg/day, while the developmental NOAEL is 30 mg/kg/day. Penta is not a developmental toxicant in a nonrodent animal model.

  17. Animal models for studying penile hemodynamics

    Institute of Scientific and Technical Information of China (English)

    HiroyaMizusawa; OsamuIshizuka

    2002-01-01

    Animal models for the study of erectile function monitoring the changes in intracavernous pressure(ICP)during penile erection was reviewed.The development of new modwls using small commercially-available experimen-tal animals,rats and mice,in the last edcade facilitated in vivo investigation of erectile physiology.The technique enabled to evaluate even subtle erectile responses by analyzing ICPand systemic blood pressure,Moreover,the method has been well improved and studies using conscious animal models without the influence of any drug or anesthesia are more appropriate in exploring the precise physiological and pharmacological mechanisms in erection.Also,more natural and physiological sexual arousal instead of electrical or pharmacological stimulation is desirable in most of the studies.This article reviewed the development of ICPstudies in rats and mice.

  18. In vivo animal studies with sugammadex

    NARCIS (Netherlands)

    Booij, L.H.D.J.; Egmond, J. van; Driessen, J.J.; Boer, H.D. de

    2009-01-01

    A review is presented of animal studies of the selective steroidal neuromuscular blocking drug binding agent sugammadex. These studies demonstrate that sugammadex is faster in onset than the currently used acetylcholinesterase inhibitors, has no muscarinic effects, and is characterised by lack of

  19. A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing - t4 report

    OpenAIRE

    Basketter, D. A.; Clewell, H.; Kimber, I; De Rossi, A.; Blaauboer, B.J.|info:eu-repo/dai/nl/068359802; Burrier, R.; Daneshian, M.; Eskes, C.; Goldberg, A.; Hasiwa, N

    2012-01-01

    Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new products (such as nanoparticles or cell therapies), the limited predictivity of traditional tests for human health effects, duration and costs of current approaches, and animal welfare considerations. The latter holds esp...

  20. Carbonyl emission and toxicity profile of diesel blends with an animal-fat biodiesel and a tire pyrolysis liquid fuel.

    Science.gov (United States)

    Ballesteros, R; Guillén-Flores, J; Martínez, J D

    2014-02-01

    In this paper, two diesel fuels, an animal-fat biodiesel and two diesel blends with the animal-fat biodiesel (50vol.%) and with a tire pyrolysis liquid (TPL) fuel (5vol.%) have been tested in a 4-cylinder, 4-stroke, turbocharged, intercooled, 2.0L Nissan diesel automotive engine (model M1D) with common-rail injection system and diesel oxidation catalyst (DOC). Carbonyl emissions have been analyzed both before and after DOC and specific reactivity of carbonyl profile has been calculated. Carbonyl sampling was carried out by means of a heated line, trapping the gas in 2,4-DNPH cartridges. The eluted content was then analyzed in an HPLC system, with UV-VIS detection. Results showed, on the one hand, an increase in carbonyl emissions with the biodiesel fraction in the fuel. On the other hand, the addition of TPL to diesel also increased carbonyl emissions. These trends were occasionally different if the emissions were studied after the DOC, as it seems to be selectivity during the oxidation process. The specific reactivity was also studied, finding a decrease with the oxygen content within the fuel molecule, although the equivalent ozone emissions slightly increased with the oxygen content. Finally, the emissions toxicity was also studied, comparing them to different parameters defined by different organizations. Depending on the point of study, emissions were above or below the established limits, although acrolein exceeded them as it has the least permissive values. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Animal venom studies: Current benefits and future developments

    Institute of Scientific and Technical Information of China (English)

    Yuri; N; Utkin

    2015-01-01

    Poisonous organisms are represented in many taxa, including kingdom Animalia. During evolution, animals have developed special organs for production and injection of venoms. Animal venoms are complex mixtures, compositions of which depend on species producing venom. The most known and studied poisonous terrestrial animals are snakes, scorpions and spiders. Among marine animals, these are jellyfishes, anemones and cone snails. The toxic substances in the venom ofthese animals are mainly of protein and peptide origin. Recent studies have indicated that the single venom may contain up to several hundred different components producing diverse physiological effects. Bites or stings by certain poisonous species result in severe envenomations leading in some cases to death. This raises the problem of bite treatment. The most effective treatment so far is the application of antivenoms. To enhance the effectiveness of such treatments, the knowledge of venom composition is needed. On the other hand, venoms contain substances with unique biological properties, which can be used both in basic science and in clinical applications. The best example of toxin application in basic science is α-bungarotoxin the discovery of which made a big impact on the studies of nicotinic acetylcholine receptor. Today compositions of venom from many species have already been examined. Based on these data, one can conclude that venoms contain a large number of individual components belonging to a limited number of structural types. Often minor changes in the amino acid sequence give rise to new biological properties. Change in the living conditions of poisonous animals lead to alterations in the composition of venoms resulting in appearance of new toxins. At the same time introduction of new methods of proteomics and genomics lead to discoveries of new compounds, which may serve as research tools or as templates for the development of novel drugs. The application of these sensitive and

  2. A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing - t4 report*.

    Science.gov (United States)

    Basketter, David A; Clewell, Harvey; Kimber, Ian; Rossi, Annamaria; Blaauboer, Bas; Burrier, Robert; Daneshian, Mardas; Eskes, Chantra; Goldberg, Alan; Hasiwa, Nina; Hoffmann, Sebastian; Jaworska, Joanna; Knudsen, Thomas B; Landsiedel, Robert; Leist, Marcel; Locke, Paul; Maxwell, Gavin; McKim, James; McVey, Emily A; Ouédraogo, Gladys; Patlewicz, Grace; Pelkonen, Olavi; Roggen, Erwin; Rovida, Costanza; Ruhdel, Irmela; Schwarz, Michael; Schepky, Andreas; Schoeters, Greet; Skinner, Nigel; Trentz, Kerstin; Turner, Marian; Vanparys, Philippe; Yager, James; Zurlo, Joanne; Hartung, Thomas

    2012-01-01

    Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new products (such as nanoparticles or cell therapies), the limited predictivity of traditional tests for human health effects, duration and costs of current approaches, and animal welfare considerations. The latter holds especially true in the context of the scheduled 2013 marketing ban on cosmetic ingredients tested for systemic toxicity. Based on a major analysis of the status of alternative methods (Adler et al., 2011) and its independent review (Hartung et al., 2011), the present report proposes a roadmap for how to overcome the acknowledged scientific gaps for the full replacement of systemic toxicity testing using animals. Five whitepapers were commissioned addressing toxicokinetics, skin sensitization, repeated-dose toxicity, carcinogenicity, and reproductive toxicity testing. An expert workshop of 35 participants from Europe and the US discussed and refined these whitepapers, which were subsequently compiled to form the present report. By prioritizing the many options to move the field forward, the expert group hopes to advance regulatory science.

  3. 40 CFR 798.4900 - Developmental toxicity study.

    Science.gov (United States)

    2010-07-01

    ... experimental animals, one dose level being used per group. Shortly before the expected date of delivery, the... CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Specific Organ/Tissue Toxicity § 798.4900... weight of test substance (g, mg) per unit weight of a test animal (e.g., mg/kg). (3) No-observed-effect...

  4. 40 CFR 798.4350 - Inhalation developmental toxicity study.

    Science.gov (United States)

    2010-07-01

    ... organogenesis, to several groups of pregnant experimental animals, one exposure level being used per group...) Test procedures—(1) Animal selection—(i) Species and strain. Testing shall be performed in at least two... SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Specific Organ/Tissue Toxicity § 798...

  5. COMPARATIVE STUDY FOR SUBCHRONIC TOXICITY OF VASELINE OIL AND GLYCELAX

    Directory of Open Access Journals (Sweden)

    A. V. Voronkov

    2016-01-01

    Full Text Available Contemporary therapeutic approaches offer a wide range of laxative agents, which are often used without a control, exceeding the regime recommended. Therefore, the comparative study for subchronic toxicity of both drugs from this group (Vaseline oil and Glycelax appears interesting.The aim of the study was the comparison of a toxic influence of 14-days application of the drugs under study.Methods. The drugs were studied in two doses: higher therapeutic, and toxic, which 10 times exceeds therapeutic dose. We used “Polispektr-8/B” electrocardiograph, BC 2800vet (Mindray hematologic veterinary analyzer, BS-380 (Mindray biochemical analyzer, CL-50 urine analyzer. After the animals autopsy we determined organs’ coefficient (heart, lungs, spleen, liver, stomach, kidneys, adrenals.Results. While studying the ECG of female rats, amplitude of R wave increased after they got Glycelax in both doses. Female rats who got Vaseline oil this index decreased at minimum dose and increased at maximum dose. After Glycelax application, male rats had an increased activity of alanine aminotransferase. After Vaseline oil application at maximum dose, female rats had alkaline phosphatase activity lowered. Female rats, which got a maximum dose of Vaseline oil had a total protein lowered. Glycelax at maximum dose increased the content of bilirubin and its fractions in male and female rats, while Vaseline oil application at maximum dose increased the content of bilirubin in female rats. Male rats which got Glycelax had hemoglobin and hematocrit level increased.Conclusion. At long-term application of Vaseline oil, animals of both genders had heart disorders with possible development of arrhythmia, hepatotoxic effect, lipid exchange dysfunction. After excessive use of Glycelax the above mentioned is added with possible hemoglobin and rheological blood properties level decrease.

  6. Application of a novel integrated toxicity testing strategy incorporating "3R" principles of animal research to evaluate the safety of a new agrochemical sulfoxaflor.

    Science.gov (United States)

    Terry, Claire; Rasoulpour, Reza J; Saghir, Shakil; Marty, Sue; Gollapudi, B Bhaskar; Billington, Richard

    2014-05-01

    Plant protection products (PPPs) and the active substance(s) contained within them are rigorously and comprehensively tested prior to registration to ensure that human health is not impacted by their use. In recent years, there has been a widespread drive to have more relevant testing strategies (e.g., ILSI/HESI-ACSA and new EU Directives), which also take account of animal welfare, including the 3R (replacement, refinement, and reduction) principles. The toxicity potential of one such new active substance, sulfoxaflor, a sulfoximine insecticide (CAS #946578-00-3), was evaluated utilizing innovative testing strategies comprising: (1) an integrated testing scheme to optimize information obtained from as few animals as possible (i.e., 3R principles) through modifications of standard protocols, such as enhanced palatability study design, to include molecular endpoints, additional neurotoxicity and immunotoxicity parameters in a subchronic toxicity study, and combining multiple test guidelines into one study protocol; (2) generation of toxicokinetic data across dose levels, sexes, study durations, species, strains and life stages, without using satellite animals, which was a first for PPP development, and (3) addition of prospective mode of action (MoA) endpoints within repeat dose toxicity studies as well as proactive inclusion of specific MoA studies as an integral part of the development program. These novel approaches to generate key data early in the safety evaluation program facilitated informed decision-making on the need for additional studies and contributed to a more relevant human health risk assessment. This supplement also contains papers which describe in more detail the approach taken to establish the MoA and human relevance framework related to toxicities elicited by sulfoxaflor in the mammalian toxicology studies: developmental toxicity in rats mediated via the fetal muscle nicotinic acetylcholine receptor (nAChR) ( Ellis-Hutchings et al. 2014 ); liver

  7. A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing - t4 report

    NARCIS (Netherlands)

    Basketter, D.A.; Clewell, H.; Kimber, I.; Rossi, A.; Blaauboer, B.J.|info:eu-repo/dai/nl/068359802; Burrier, R.; Daneshian, M.; Eskes, C.; Goldberg, A.; Hasiwa, N.

    2012-01-01

    Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new products (such as

  8. Development and Application of In Vitro Models for Screening Drugs and Environmental Chemicals that Predict Toxicity in Animals and Humans

    Science.gov (United States)

    Development and Application of In Vitro Models for Screening Drugs and Environmental Chemicals that Predict Toxicity in Animals and Humans (Presented by James McKim, Ph.D., DABT, Founder and Chief Science Officer, CeeTox) (5/25/2012)

  9. A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing - t4 report

    NARCIS (Netherlands)

    Basketter, D.A.; Clewell, H.; Kimber, I.; Rossi, A.; Blaauboer, B.J.; Burrier, R.; Daneshian, M.; Eskes, C.; Goldberg, A.; Hasiwa, N.

    2012-01-01

    Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new products (such as nanopa

  10. Replacing animal experiments in developmental toxicity testing of phenols by combining in vitro assays with physiologically based kinetic (PBK) modelling

    NARCIS (Netherlands)

    Strikwold, Marije

    2016-01-01

    Many efforts have been undertaken over the past decades to develop in vitro tests for a wide range of toxicological endpoints as an alternative to animal testing. The principle application of in vitro toxicity assays still lies in the hazard assessment and the prioritisation of chemicals for further

  11. Estimation of bisphenol A-Human toxicity by 3D cell culture arrays, high throughput alternatives to animal tests.

    Science.gov (United States)

    Lee, Dong Woo; Oh, Woo-Yeon; Yi, Sang Hyun; Ku, Bosung; Lee, Moo-Yeal; Cho, Yoon Hee; Yang, Mihi

    2016-09-30

    Bisphenol A (BPA) has been widely used for manufacturing polycarbonate plastics and epoxy resins and has been extensively tested in animals to predict human toxicity. In order to reduce the use of animals for toxicity assessment and provide further accurate information on BPA toxicity in humans, we encapsulated Hep3B human hepatoma cells in alginate and cultured them in three dimensions (3D) on a micropillar chip coupled to a panel of metabolic enzymes on a microwell chip. As a result, we were able to assess the toxicity of BPA under various metabolic enzyme conditions using a high-throughput and micro assay; sample volumes were nearly 2,000 times less than that required for a 96-well plate. We applied a total of 28 different enzymes to each chip, including 10 cytochrome P450s (CYP450s), 10 UDP-glycosyltransferases (UGTs), 3 sulfotransferases (SULTs), alcohol dehydrogenase (ADH), and aldehyde dehydrogenase 2 (ALDH2). Phase I enzyme mixtures, phase II enzyme mixtures, and a combination of phase I and phase II enzymes were also applied to the chip. BPA toxicity was higher in samples containing CYP2E1 than controls, which contained no enzymes (IC50, 184±16μM and 270±25.8μM, respectively, panimal testing for estimating BPA toxicity via human metabolic systems. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. An innovative approach to sampling complex industrial emissions for use in animal toxicity tests: application to iron casting operations.

    Science.gov (United States)

    Palmer, W G; Scholz, R C; Moorman, W J

    1983-03-01

    Sampling of complex mixtures of airborne contaminants for chronic animal toxicity tests often involves numerous sampling devices, requires extensive sampling time, and yields forms of collected materials unsuitable for administration to animals. A method is described which used a high volume, wet venturi scrubber for collection of respirable fractions of emissions from iron foundry casting operations. The construction and operation of the sampler are presented along with collection efficiency data and its application to the preparation of large quantities of samples to be administered to animals by intratracheal instillation.

  13. Fungicidal activity of AKWATON and in vitro assessment of its toxic effects on animal cells.

    Science.gov (United States)

    Oulé, Mathias Kégnon; Staines, Kenton; Lightly, Tasia; Roberts, Loren; Traoré, Yannick Léandre; Dickman, Michael; Bernier, Anne-Marie; Diop, Lamine

    2015-01-01

    Acquired superficial fungal infections are among the most common infections. It is necessary to create new effective and non-toxic disinfectants. AKWATON is a new disinfectant of the polymeric guanidine family. Its fungicidal activity against Trichophyton mentagrophytes and its in vitro toxicity assessment were determined in this study. The MIC, minimum fungicidal concentration (MFC) and time required for its fungicidal activity at the MFC were evaluated using the official methods of analysis of the Association of Official Analytical Chemists, with modifications as recommended by the Canadian General Standards Board. The toxic effects of AKWATON and of four commercial disinfectants were evaluated on rat pancreatic (C2C12) and muscle (RnM5F) cells, using the trypan blue and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] methods. The MIC, MFC and time required for the fungicidal activity of AKWATON at the MFC were 0.025 % (w/v), 0.045 % (w/v) and 2.5 min, respectively. Cell cultures and the different tests carried out showed that the AKWATON-based disinfectant killed fewer cells than the commercial disinfectants, sparing 80 % of C2C12 cells and 65 % of RnM5F cells, whilst some of the well-known disinfectants currently on the market killed 85-100 % of cells. This study demonstrates that AKWATON has great potential as an odourless, colourless, non-corrosive and safe disinfectant for use in hospitals, the agriculture industry, farming and household facilities.

  14. Avisalmvac: evaluation studies of stability and toxicity

    Directory of Open Access Journals (Sweden)

    Daniela Botus,

    2008-12-01

    Full Text Available In Pasteur Institute laboratories there was developed AVISALMVAC, a vaccine against avian Salmonella, a biological product that contains S. enteritidis and S. typhimurium bacterin, with oil adjuvant. This paper presents the results of the studies regarding the stability and toxicity evaluation of this vaccine stored under conditions recommended by the manufacturer (2-80C at the end of the period of validity. The vaccine stability was assessed by serological and histopathological analysis of samples from SPF chickens vaccinated with the product at the end of the period of validity. The study of Avisalmvac toxicity was carried out by inoculation of the product or its components on Vero cell monolayer, and the effects were microscopically recorded or by MTT test, applied at 6 days post-inoculation. Antibody titers recorded at 2 and 3 weeks post vaccination demonstrated the vaccine ability (used after an year since manufacture to induce synthesis of specific antibodies and therefore, the product stability was proven. Histopathological examinations carried out on samples taken at 18 days post vaccinationfrom the vaccination site (skeletal muscle and skin and spleen, did not show any lesions associated to vaccination with Avisalmvac. The cytotoxicity analysis made by inoculating the vaccine or its components on Vero cell monolayer and the microscopic examination did not record visible cytopathic effects for any vaccine dilutions or vaccine components. The cell metabolism evaluation by MTT assay made at 6 days after vaccine/vaccine components inoculation on Vero monolayer, shown the ability of the vaccine and oil adjuvant to stimulate cell metabolism, and a certain degree of toxicity / inhibition of dehydrogenase metabolism associated to one of emulsifier but at dilutions higher than those used in the vaccine formula.

  15. Subacute(90Days) Oral Toxicity Studies of Kombucha Tea

    Institute of Scientific and Technical Information of China (English)

    R.VIJAYARAGHAVAN; MANINDERSINGH; 等

    2000-01-01

    Kombucha tes(KT) is a popular health beverage and is used as an alternative therapy,KT is prepared by placing the kombucha culture in solution of tea and sugar and allowing to ferment,The inoculum is a fungus consisting of symbiotic colony of yeast and bacteria.KT is consumed in several coutries and is believed to have prophylactic and therapeutic benefits in a wide variety of ailments,viz.,intestinal disorders,arthritis,ageing and stiumulation of immunological system.Though KT is used in several parts of the world its eneficial effects and adverse effects have not been scientifically evaluated.Since there are no animal toxicological data on KT,subacute oral toxicity study was carried out.Five goups of rats were maintained:(a) control group given tap water orally,(b) KT given 2ml/kg orally,(c)plain tea(PT) given 2ml/kg orally,(d)KT given in drinking water,1%(v/v)and (e)PT given indrinking water,1%(v/v).The rats were given this treatment daily for a period of 90 days,Weekly records of weight,feed intake,water intake and general behaviour were monitored.There was no significant difference in the growth of the animals as evidenced by the progrssive body weight change.The organ to body weight ration and histologuical evaluation did not show any toxic signs.The haematological and biochemical variables,were within the clinical limits.The study indicates that rats fed KT for 90 day showed no toxic effects.

  16. Duration of Acute and Chronic Toxicity Testing in Animals (ICH S4A and S4B)

    DEFF Research Database (Denmark)

    Spindler, Per; Van Cauteren, Herman

    2013-01-01

    To support approval of pharmaceuticals for long term use in humans it is required that product safety is supported by acute and chronic toxicity studies in rodents and non-rodents. The duration of acute toxicity studies (S4A) and chronic rodent studies (S4B) were harmonised between the three ICH ...

  17. Invited review: Efficacy, metabolism, and toxic responses to chlorate salts in food and laboratory animals.

    Science.gov (United States)

    Smith, D J; Oliver, C E; Taylor, J B; Anderson, R C

    2012-11-01

    For over 100 yr, scientists have explored uses of sodium chlorate in agricultural applications. Sodium chlorate is a strong oxidizer, and thus can be very hazardous when not handled accordingly. Nevertheless, late 19th century agriculturists and scientists attempted to exploit the chemical properties of sodium chlorate as an herbicide and food preservative. It is the herbicidal utility that led to subsequent use of sodium chlorate in the agricultural industry since then. However, in 2000, USDA-ARS scientists proposed a new and targeted use of sodium chlorate against enterobacteria in food animal production. Specifically, when orally dosed in to cattle (Bos taurus), swine (Sus scrofa), broilers (Gallus gallus), turkeys (Meleagris gallopavo), and sheep (Ovis aries), chlorate reduced the fecal shedding of common enteropathogens of the Enterobacteriaceae family. Subsequent to this discovery, the efficacy of chlorate salts has been demonstrated in numerous production classes within species. Doses of sodium chlorate as low as 30 mg/kg BW, but typically 50 to 150 mg/kg BW, have been used to demonstrate efficacy against pathogens. Single or short-duration (food animals. In all species studied to date, the major biotransformation product of chlorate is chloride ion; chlorite is not present in tissues or excreta of chlorate dosed animals. Chlorate is rapidly eliminated in ruminants and nonruminants, primarily in urine; likewise, residual chlorate in tissues depletes rapidly. Application of any new chemical entity to food animal production carries with it a responsibility to understand adverse reactions that intended and nonintended exposures may have in target and (or) nontarget animals and an understanding of the pathways of elimination that occur after exposure. Therefore, the purpose of this review is to summarize the published data regarding the efficacy, metabolism, and toxicology of chlorate salts in target (livestock) and nontarget species.

  18. Inaugurating the Study of Animal Metacognition

    OpenAIRE

    Smith, J. David

    2010-01-01

    Metacognition—the ability to monitor and control one’s own cognition—is a sophisticated ability that reveals humans’ reflective mind and consciousness. Researchers have begun to explore whether animals share humans’ metacognitive capacity. This article reprises the original study that explored metacognition across species. A captive dolphin performed an auditory pitch-discrimination task using High/Low discrimination responses and an Uncertainty response with which he could decline to complet...

  19. Transcriptomic studies on liver toxicity of acetaminophen.

    Science.gov (United States)

    Toska, Endrit; Zagorsky, Robert; Figler, Bryan; Cheng, Feng

    2014-09-01

    Acetaminophen is widely used as a pain reliever and to reduce fever. At high doses, it can cause severe hepatotoxicity. Acetaminophen overdose has become the leading cause of acute liver failure in the US. The mechanisms for acetaminophen-induced liver injury are unclear. Transcriptomic studies can identify the changes in expression of thousands of genes when exposed to supratherapeutic doses of acetaminophen. These studies elucidated the mechanism of acetaminophen-induced hepatotoxicity and also provide insight into future development of diagnosis and treatment options for acetaminophen-induced acute liver failure. The following is a brief overview of some recent transcriptomic studies and gene-expression-based prediction models on liver toxicity induced by acetaminophen.

  20. Multispecies animal investigation on biodistribution, pharmacokinetics and toxicity of {sup 177}Lu-EDTMP, a potential bone pain palliation agent

    Energy Technology Data Exchange (ETDEWEB)

    Mathe, Domokos [Department of Applied Radioisotopes and Animal Experimentation, National ' Frederic Joliot-Curie' Institute of Radiobiology and Radiohygiene, H-1221 Budapest (Hungary)], E-mail: mdomokos@hp.osski.hu; Balogh, Lajos; Polyak, Andras; Kiraly, Reka [Department of Applied Radioisotopes and Animal Experimentation, National ' Frederic Joliot-Curie' Institute of Radiobiology and Radiohygiene, H-1221 Budapest (Hungary); Marian, Terez [Institute of Nuclear Medicine, Debrecen University, Debrecen (Hungary); Pawlak, Dariusz [Institute of Atomic Energy, Radioisotope Centre POLATOM, Swierk-Otwock (Poland); Zaknun, John J.; Pillai, Maroor R.A. [International Atomic Energy Agency (IAEA), Vienna (Austria); Janoki, Gyozo A. [Department of Applied Radioisotopes and Animal Experimentation, National ' Frederic Joliot-Curie' Institute of Radiobiology and Radiohygiene, H-1221 Budapest (Hungary)

    2010-02-15

    Introduction: Radionuclide therapy (RNT) is an effective method for bone pain palliation in patients suffering from bone metastasis. Due to the long half-life, easy production and relatively low {beta}- energy, {sup 177}Lu [T{sub 1/2}=6.73 days, E{sub {beta}}{sub max}=497 keV, E{sub {gamma}}=113 keV (6.4%), 208 keV (11%)]-based radiopharmaceuticals offer logistical advantage for wider use. This paper reports the results of a multispecies biodistribution and toxicity studies of {sup 177}Lu-EDTMP to collect preclinical data for starting human clinical trials. Methods: {sup 177}Lu-EDTMP with radiochemical purity greater than 99% was formulated by using a lyophilized kit of EDTMP (35 mg of EDTMP, 5.72 g of CaO and 14.1 mg of NaOH). Biodistribution studies were conducted in mice and rabbits. Small animal imaging was performed using NanoSPECT/CT (Mediso, Ltd., Hungary) and digital autoradiography. Gamma camera imaging was done in rabbits and dogs. Four levels of activity (9.25 through 37 MBq/kg body weight) of {sup 177}Lu-EDTMP were injected in four groups of three dogs each to study the toxicological effects. Results: {sup 177}Lu-EDTMP accumulated almost exclusively in the skeletal system (peak ca. 41% of the injected activity in bone with terminal elimination half-life of 2130 and 1870 h in mice and rabbits, respectively) with a peak uptake during 1-3 h. Excretion of the radiopharmaceutical was through the urinary system. Imaging studies showed that all species (mouse, rat, rabbit and dog) take up the compound in regions of remodeling bone, while kidney retention is not visible after 1 day postinjection (pi). In dogs, the highest applied activity (37 MBq/kg body weight) led to a moderate decrease in platelet concentration (mean, 160 g/L) at 1 week pi with no toxicity. Conclusion: The protracted effective half-life of {sup 177}Lu-EDTMP in bone supports that modifying the EDTMP molecule by introducing {sup 177}Lu does not alter its biological behaviour as a specific bone

  1. [Advance in study on zearalenone's toxicity and determination].

    Science.gov (United States)

    He, Qing-Hua; Xu, Yang

    2005-07-01

    The article is intended to introduce the zearalenone's toxicity, determination methods and prevention. Zearalenone is one of the most widely distributed mycotoxins produces by Fusarium Species, it is harm to animals and human. And it can induce human liver cancer,carcinoma of tesis esophagus cancer. Now we use high-performance liquid chromatography, gas chromatography, thin layer chromatography, non-toxicity determinations to detect it.

  2. ACUTE AND SUB ACUTE TOXICITY STUDY ON SIDDHA DRUG VELVANGA PARPAM

    Directory of Open Access Journals (Sweden)

    K. Samraj*, K. Kanagavalli , P. Sathiya Rajeswaran and P. Parthiban

    2013-11-01

    Full Text Available Benign Prostatic Hyperplasia (BPH is a common progressive disease among men, with an incidence that is high among elderly. Velvanga parpam (VP has been employed as traditional remedy for Benign Prostatic Hyperplasia (BPH which is a herbo mineral formulation. As a mandate, steps were taken to evaluate safety profile of VP in rats and mice following OECD guidelines. Acute toxicity studies, different doses of VP were administered orally to rats once daily for one week. Sub-acute toxicity studies were carried in four different groups in which VP was administrated orally to rats once daily for 28 days in various doses ranging from 2.5, 5, 10 Mg/kg for mice respectively. Detailed hematological, biochemical, necropsy and histopathological evaluation of organs was performed for all animals. The VP was well tolerated and no toxic manifestations were seen in any animal. Histopathological analysis revealed that Spleen, Testes, Pancreas, Lung, Liver, Brain, Heart, Stomach, Intestine, Bone, Ovary, and Kidney tissues of treated groups did not show any signs of toxicity. Mortality observed in highdose. The VP was found to be safe in animals. No toxic effect was observed up to 5mg/kg of Velvanga parpam in acute and sub-acute toxicity studies.

  3. Liposomal butamben gel formulations: toxicity assays and topical anesthesia in an animal model.

    Science.gov (United States)

    Cereda, Cintia Maria Saia; Guilherme, Viviane Aparecida; Alkschbirs, Melissa Inger; de Brito Junior, Rui Barbosa; Tofoli, Giovana Radomille; Franz-Montan, Michelle; de Araujo, Daniele Ribeiro; de Paula, Eneida

    2017-03-01

    The aim of this study was to evaluate the in vitro cytotoxicity and the in vivo analgesic effect and local toxicity of the local anesthetic butamben (BTB) encapsulated in conventional or elastic liposomes incorporated in gel formulations. The results showed that both gel formulations of liposomal BTB reduced the cytotoxicity (p < 0.001; one-way ANOVA/Tukey's test) and increased the topical analgesic effect (p < 0.05; one-way ANOVA/Tukey's test) of butamben, compared to plain BTB gel. The gel formulations presented good rheological properties, and stability assays detected no differences in physicochemical stability up to 30 d after preparation. Moreover, histological assessment revealed no morphological changes in rat skin after application of any of the gel formulations tested.

  4. Study Circles and Socio-cultural Animation

    Directory of Open Access Journals (Sweden)

    Vilma Malečkar

    2001-12-01

    Full Text Available Informal learning and participating in study circles is a way of applying the ideas of socio-cultural animation. It is based on the assumption that within a society there are mechanisms that institutions don't comprise and therefore don't fulfil various, often urgent needs deriving from everyday life and the community. What is going on here is identifying and solving burning problems; some of them have already become an integral part of the way of living in a community. Study circles as an informal phenomenon in Slovenia create new possibilities of social activities based on common learning and participating in a community.

  5. An animal model to study regenerative endodontics.

    Science.gov (United States)

    Torabinejad, Mahmoud; Corr, Robert; Buhrley, Matthew; Wright, Kenneth; Shabahang, Shahrokh

    2011-02-01

    A growing body of evidence is demonstrating the possibility for regeneration of tissues within the pulp space and continued root development in teeth with necrotic pulps and open apices. There are areas of research related to regenerative endodontics that need to be investigated in an animal model. The purpose of this study was to investigate ferret cuspid teeth as a model to investigate factors involved in regenerative endodontics. Six young male ferrets between the ages of 36-133 days were used in this investigation. Each animal was anesthetized and perfused with 10% buffered formalin. Block sections including the mandibular and maxillary cuspid teeth and their surrounding periapical tissues were obtained, radiographed, decalcified, sectioned, and stained with hematoxylin-eosin to determine various stages of apical closure in these teeth. The permanent mandibular and maxillary cuspid teeth with open apices erupted approximately 50 days after birth. Initial signs of closure of the apical foramen in these teeth were observed between 90-110 days. Complete apical closure was observed in the cuspid teeth when the animals were 133 days old. Based on the experiment, ferret cuspid teeth can be used to investigate various factors involved in regenerative endodontics that cannot be tested in human subjects. The most appropriate time to conduct the experiments would be when the ferrets are between the ages of 50 and 90 days. Copyright © 2011. Published by Elsevier Inc.

  6. Acute and repeated dose toxicity studies of different β-cyclodextrin-based nanosponge formulations.

    Science.gov (United States)

    Shende, Pravin; Kulkarni, Yogesh A; Gaud, R S; Deshmukh, Kiran; Cavalli, Roberta; Trotta, Francesco; Caldera, Fabrizio

    2015-05-01

    Nanosponges (NS) show promising results in different fields such as medicine, agriculture, water purification, fire engineering and so on. The present study was designed to evaluate toxicity of different NS formulations (namely, S1-S6) synthesized with different cross-linking agents such as carbonyl diimidazole, pyromellitic dianhydride and hexamethylene diisocynate; and preparation methods in experimental animals. Acute and repeated dose toxicity studies of formulations were carried out as per OECD guidelines 423 and 407, respectively. For acute toxicity study, formulations were administered to female rats at doses of 300 and 2000 mg/kg orally. The general behaviour of the rats was continuously monitored for 1 h after dosing, periodically during the first 24 h and daily thereafter for a total of 14 days. On day 14, animals were fasted overnight, weighed, and sacrificed. After sacrification, animals were subjected to necropsy. For repeated dose toxicity study, rats of either sex were orally administered with formulations at the dose of 300 mg/kg per day for a period of 28 days. The maximally tolerated dose of all formulations was found to be 2000 mg/kg. Repeated administration of formulations for 28 days did not show any significant changes in haematological and biochemical parameters in experimental animals. These results indicate that the formulations are safe, when tested in experimental animals.

  7. Toxicity Studies of Ethyl Maltol and Iron Complexes in Mice.

    Science.gov (United States)

    Li, Zhen; Lu, Jieli; Wu, Chonghui; Pang, Quanhai; Zhu, Zhiwei; Nan, Ruipeng; Du, Ruochen; Chen, Jia

    2017-01-01

    Ethyl maltol and iron complexes are products of ethyl maltol and the iron found in the cooking pots used to prepare the Chinese dish, hot-pot. Because their safety is undocumented, the toxicity study of ethyl maltol and iron complexes was conducted in male and female Kunming (KM) mice. The animal study was designed based on the preliminary study conducted to determine the median lethal dose (LD50). The doses used in the study were 0, 1/81, 1/27, 1/9, and 1/3 of the LD50 (mg kg body weight (BW)(-1) day(-1)) dissolved in the water. The oral LD50 of the ethyl maltol and iron complexes was determined to be 743.88 mg kg BW(-1) in mice. The ethyl maltol and iron complexes targeted the endocrine organs including the liver and kidneys following the 90 D oral exposure. Based on the haematological data, the lowest-observed-adverse-effect level (LOAEL) of the ethyl maltol and iron complexes was determined to be 1/81 LD50 (9.18 mg kg BW(-1) day(-1)) in both male and female mice. Therefore, we suggest that alternative strategies for preparing the hot-pot, including the use of non-Fe-based cookware, need to be developed and encouraged to avoid the formation of the potentially toxic complexes.

  8. Krill Products: An Overview of Animal Studies

    Directory of Open Access Journals (Sweden)

    Lena Burri

    2015-05-01

    Full Text Available Many animal studies have been performed with krill oil (KO and this review aims to summarize their findings and give insight into the mechanism of action of KO. Animal models that have been used in studies with KO include obesity, depression, myocardial infarction, chronic low-grade and ulcerative inflammation and are described in detail. Moreover, studies with KO in the form of krill powder (KP and krill protein concentrate (KPC as a mix of lipids and proteins are mentioned and compared to the effects of KO. In addition, differences in tissue uptake of the long-chain omega-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA, when delivered in either phospholipid or triglyceride form, are addressed and the differential impact the delivery form has on gene expression profiles is explained. In our outlook, we try to highlight the potential of KO and KP supplementation in clinical settings and discuss health segments that have a high potential of showing krill product specific health benefits and warrant further clinical investigations.

  9. Pulmonary Toxicity Studies of Lunar Dust in Rodents

    Science.gov (United States)

    Lam, Chiu-Wing; James, John T.

    2012-01-01

    NASA has been contemplating returning astronauts to the moon for long-duration habitation and research and using it as a stepping-stone to Mars. Other spacefaring nations are planning to send humans to the moon for the first time. The surface of the moon is covered by a layer of fine dust. Fine terrestrial dusts, if inhaled, are known to pose a health risk to humans. Some Apollo crews briefly exposed to moon dust that adhered to spacesuits and became airborne in the Lunar Module reported eye and throat irritation. The habitable area of any lunar landing vehicle or outpost would inevitably become contaminated with lunar dust. To assess the health risks of exposure of humans to airborne lunar dust, we evaluated the toxicity of Apollo 14 moon dust in animal lungs. Studies of the pulmonary toxicity of a dust are generally first done by intratracheal instillation (ITI) of aqueous suspensions of the test dust into the lungs of rodents. If a test dust is irritating or cytotoxic to the lungs, the alveolar macrophages, after phagocytizing the dust particles, will release cellular messengers to recruit white blood cells (WBCs) and to induce dilation of blood capillary walls to make them porous, allowing the WBCs to gain access to the alveolar space. The dilation of capillary walls also allows serum proteins and water entering the lung. Besides altering capillary integrity, a toxic dust can also directly kill the cells that come into contact with it or ingest it, after which the dead cells would release their contents, including lactate dehydrogenase (a common enzyme marker of cell death or tissue damage). In the treated animals, we lavaged the lungs 1 and 4 weeks after the dust instillation and measured the concentrations of these biomarkers of toxicity in the bronchioalveolar lavage fluids to determine the toxicity of the dust. To assess whether the inflammation and cellular injury observed in the biomarker study would lead to persistent or progressive histopathological

  10. Multi-endpoint, high-throughput study of nanomaterial toxicity in Caenorhabditis elegans.

    Science.gov (United States)

    Jung, Sang-Kyu; Qu, Xiaolei; Aleman-Meza, Boanerges; Wang, Tianxiao; Riepe, Celeste; Liu, Zheng; Li, Qilin; Zhong, Weiwei

    2015-02-17

    The booming nanotechnology industry has raised public concerns about the environmental health and safety impact of engineered nanomaterials (ENMs). High-throughput assays are needed to obtain toxicity data for the rapidly increasing number of ENMs. Here we present a suite of high-throughput methods to study nanotoxicity in intact animals using Caenorhabditis elegans as a model. At the population level, our system measures food consumption of thousands of animals to evaluate population fitness. At the organism level, our automated system analyzes hundreds of individual animals for body length, locomotion speed, and lifespan. To demonstrate the utility of our system, we applied this technology to test the toxicity of 20 nanomaterials at four concentrations. Only fullerene nanoparticles (nC60), fullerol, TiO2, and CeO2 showed little or no toxicity. Various degrees of toxicity were detected from different forms of carbon nanotubes, graphene, carbon black, Ag, and fumed SiO2 nanoparticles. Aminofullerene and ultraviolet-irradiated nC60 also showed small but significant toxicity. We further investigated the effects of nanomaterial size, shape, surface chemistry, and exposure conditions on toxicity. Our data are publicly available at the open-access nanotoxicity database www.QuantWorm.org/nano.

  11. A multi-endpoint, high-throughput study of nanomaterial toxicity in Caenorhabditis elegans

    Science.gov (United States)

    Jung, Sang-Kyu; Qu, Xiaolei; Aleman-Meza, Boanerges; Wang, Tianxiao; Riepe, Celeste; Liu, Zheng; Li, Qilin; Zhong, Weiwei

    2015-01-01

    The booming nanotech industry has raised public concerns about the environmental health and safety impact of engineered nanomaterials (ENMs). High-throughput assays are needed to obtain toxicity data for the rapidly increasing number of ENMs. Here we present a suite of high-throughput methods to study nanotoxicity in intact animals using Caenorhabditis elegans as a model. At the population level, our system measures food consumption of thousands of animals to evaluate population fitness. At the organism level, our automated system analyzes hundreds of individual animals for body length, locomotion speed, and lifespan. To demonstrate the utility of our system, we applied this technology to test the toxicity of 20 nanomaterials under four concentrations. Only fullerene nanoparticles (nC60), fullerol, TiO2, and CeO2 showed little or no toxicity. Various degrees of toxicity were detected from different forms of carbon nanotubes, graphene, carbon black, Ag, and fumed SiO2 nanoparticles. Aminofullerene and UV irradiated nC60 also showed small but significant toxicity. We further investigated the effects of nanomaterial size, shape, surface chemistry, and exposure conditions on toxicity. Our data are publicly available at the open-access nanotoxicity database www.QuantWorm.org/nano. PMID:25611253

  12. A multi-endpoint, high-throughput study of nanomaterial toxicity in Caenorhabditis elegans

    OpenAIRE

    Jung, Sang-Kyu; Qu, Xiaolei; Aleman-Meza, Boanerges; Wang, Tianxiao; Riepe, Celeste; Liu, Zheng; Li, Qilin; Zhong, Weiwei

    2015-01-01

    The booming nanotech industry has raised public concerns about the environmental health and safety impact of engineered nanomaterials (ENMs). High-throughput assays are needed to obtain toxicity data for the rapidly increasing number of ENMs. Here we present a suite of high-throughput methods to study nanotoxicity in intact animals using Caenorhabditis elegans as a model. At the population level, our system measures food consumption of thousands of animals to evaluate population fitness. At t...

  13. Inaugurating the Study of Animal Metacognition.

    Science.gov (United States)

    Smith, J David

    2010-01-01

    Metacognition-the ability to monitor and control one's own cognition-is a sophisticated ability that reveals humans' reflective mind and consciousness. Researchers have begun to explore whether animals share humans' metacognitive capacity. This article reprises the original study that explored metacognition across species. A captive dolphin performed an auditory pitch-discrimination task using High/Low discrimination responses and an Uncertainty response with which he could decline to complete any trials he chose. He selectively declined the difficult trials near his discriminative threshold-just as humans do. This comparative exploration of metacognition required a trial-intensive titration of perceptual threshold and the training of a distinctive behavioral response. It could not have been conducted in the wild, though the naturalistic observation of dolphin uncertainty behaviors and risk-management strategies would no doubt yield complementary insights. The dolphin study inaugurated a new area of cross-species research. This research area opens a new window on reflective mind in animals, illuminates the phylogenetic emergence of metacognition, and may reveal the antecedents of human consciousness.

  14. Safety studies of homoeopathic drugs in acute, sub-acute and chronic toxicity in rats

    Directory of Open Access Journals (Sweden)

    Surender Singh

    2017-01-01

    Full Text Available Background: Homoeopathic drugs are frequently recommended in day to day life as therapeutic agents by homoeopathic practitioners. However, safety of homoeopathic drugs remains a challenge because of the high variability of chemical components involved. Aim: The objective of the present study was to investigate the acute, subacute, and chronic oral toxicity of different homoeopathic drugs (Ferrum phosphoricum 3X, Ferrum phosphoricum 6X, Calcarea phosphoricum 6X, and Magnesium phosphoricum 6X in experimental models. Materials and Methods: In acute oral toxicity study, homoeopathic drugs were administered orally at 2000mg/kg body weight, and animals were observed for toxic symptoms till 10 days as per the OECD guidelines. For subacute and chronic toxicity study, homoeopathic drugs were administered for 28 and 180 days, respectively, as per the OECD guidelines. At the end of 28 and 180 days, the animals were sacrificed and toxicity parameters were assessed. Histopathological evaluation of different organs was also performed to assess any toxicity. Results: In acute toxicity study, no mortality was found at a dose of 2000 mg/kg which indicates that oral LD50of homoeopathic drugs were more than 2000 mg/kg. The administration of drugs at a dose of 70 mg/kg body weight for 28 and 180 days did not produce any significant change in haematological and biochemical parameters of male and female rats as compared to normal control group. No pathological changes were observed in histology of various organs of treated rats as compared to normal control animals. Conclusion: These homoeopathic drugs are safe & produce no toxicity when administered for longer duration.

  15. In vivo toxicity study of Lantana camara

    Institute of Scientific and Technical Information of China (English)

    Badakhshan Mahdi Pour; Sreenivasan Sasidharan

    2011-01-01

    Objective: To investigate the toxicity of methanol extract of various parts (Root, Stem, Leaf, Flower and Fruit) of Lantana camara(L. Camara) in Artemia salina. Methods: The methanol extracts of L. camara were tested for in vivo brine shrimp lethality assay. Results: All the tested extract exhibited very low toxicity on brine shrimp larva. The results showed that the root extract was the most toxic part of L. camara and may have potential as anticancer agent. Conclusions:Methanolic extract of L. camara is relatively safe on short-term exposure.

  16. Metabolism and toxicity studies supporting the safety of rebaudioside D.

    Science.gov (United States)

    Nikiforov, Andrey I; Rihner, Marisa O; Eapen, Alex K; Thomas, Jennifer A

    2013-07-01

    Rebaudioside D (Reb D) is one of the several glycosides found in the leaves of Stevia rebaudiana (Bertoni) Bertoni (Compositae) which has been identified as a potential sweetener. The metabolism of Reb A and Reb D was evaluated in various in vitro matrices (simulated gastrointestinal fluids, rat liver microsomes, and rat cecal contents) and through analysis of plasma collected from rats in a dietary toxicity study. Reb A and Reb D showed similar stability when exposed to simulated stomach and small intestine fluids, with susceptibility to hydrolytic degradation by enteric bacteria collected from the cecum. Incubations with rat liver microsomes indicated that neither compound is expected to be metabolized by the liver enzymes. Plasma concentrations of Reb D, Reb A, and/or the final hydrolysis product of each compound, free/conjugated steviol, were consistent between animals administered either Reb D or Reb A in the diet. A repeated exposure dietary toxicity study was conducted to compare the safety of Reb D, when administered at target exposure levels of 500, 1000, and 2000 mg/kg body weight (bw)/d to Sprague-Dawley rats for 28 days, to that of Reb A administered at a target exposure level of 2000 mg/kg bw/d. There were no treatment-related effects on the general condition and behavior of the animals and no toxicologically relevant, treatment-related effects on hematology, serum chemistry, or urinalysis. Macroscopic and microscopic findings revealed no treatment-related effects on any organ evaluated. Results were comparable between the group administered 2000 mg/kg/d Reb D and the group administered 2000 mg/kg/d Reb A.

  17. 40 CFR 799.9305 - TSCA Repeated dose 28-day oral toxicity study in rodents.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 31 2010-07-01 2010-07-01 true TSCA Repeated dose 28-day oral toxicity study in rodents. 799.9305 Section 799.9305 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... strains of young healthy adult animals should be employed. The females should be nulliparous and...

  18. Animal models for HCV and HBV studies

    Directory of Open Access Journals (Sweden)

    Isabelle Chemin

    2007-02-01

    develop fulminant hepatitis, acute hepatitis, or chronic liver disease after adoptive transfer, and others spontaneously develop hepatocellular carcinoma (HCC. Among HCV transgenic mice, most develop no disease, but acute hepatitis has been observed in one model, and HCC in another. Although mice are not susceptible to HBV and HCV, their ability to replicate these viruses and to develop liver diseases characteristic of human infections provides opportunities to study pathogenesis and develop novel therapeutics In the search for the mechanism of hepatocarcinogenesis in hepatitis viral infection, two viral proteins, the core protein of hepatitis C virus (HCV and the HBx protein of hepatitis B virus (HBV, have been shown to possess oncogenic potential through transgenic mouse studies, indicating the direct involvement of the hepatitis viruses in hepatocarcinogenesis.

    This may explain the very high frequency of HCC in patients with HCV or HBV infection.

    Chimpanzees remain the only recognized animal model for the study of hepatitis C virus (HCV. Studies performed in chimpanzees played a critical role in the discovery of HCV and are continuing to play an essential role in defining the natural history of this important human pathogen. In the absence of a reproducible cell culture system, the infectivity titer of HCV challenge pools can be determined only in chimpanzees.

    Recent studies in chimpanzees have provided new insight into the nature of host immune responses-particularly the intrahepatic responses-following primary and secondary experimental HCV infections. The immunogenicity and efficacy of vaccine candidates against HCV can be tested only in chimpanzees. Finally, it would not have been possible to demonstrate

  19. Assessment of the potential toxicity of a linear alkylbenzene sulfonate (LAS) to freshwater animal life by means of cladoceran bioassays.

    Science.gov (United States)

    Coelho, Katiuscia da Silva; Rocha, Odete

    2010-04-01

    The acute and chronic toxic effects of LAS on the cladocerans Daphnia similis, Ceriodaphnia dubia and Ceriodaphnia silvestrii were tested. Both types of toxicity bioassays and the methods of culture and stock maintenance of the test organisms conformed to the recommendations of ABNT (Brazilian Society of Technical Standards), which closely follow the standard methods of USEPA. The results obtained for EC(50) (48 h) were: 14.17 mg L(-1) for D. similis, 11.84 mg L(-1) for C. dubia and 13.52 mg L(-1) for C. silvestrii. In the chronic toxicity tests performed on C. dubia and C. silvestrii, there was a significant decrease in the fecundity of the exposed animals; the value of NOEC for C. dubia and C. silvestrii were 1.00 mg L(-1) and 2.50 mg L(-1), respectively. Cladoceran bioassays provided evidence that LAS concentration as low as 1.00 mg L(-1) can damage invertebrate animal life in freshwaters, concentrations that can be found in many eutrophic rivers and reservoirs.

  20. Resistance to toxic plants: The right animal in the right pasture at the right time

    Science.gov (United States)

    Neurotoxic poisonous plants negatively impact livestock on many western rangelands, which results in annual economic losses of millions of dollars from animal deaths, increased management and treatment costs, and if animals are deferred from grazing, the underutilization of otherwise highly nutritio...

  1. Animator

    Science.gov (United States)

    Tech Directions, 2008

    2008-01-01

    Art and animation work is the most significant part of electronic game development, but is also found in television commercials, computer programs, the Internet, comic books, and in just about every visual media imaginable. It is the part of the project that makes an abstract design idea concrete and visible. Animators create the motion of life in…

  2. Animals

    Energy Technology Data Exchange (ETDEWEB)

    Skuterud, L.; Strand, P. [Norwegian Radiation Protection Authority (Norway); Howard, B.J. [Inst. of Terrestrial Ecology (United Kingdom)

    1997-10-01

    The radionuclides of most concern with respect to contamination of animals after a nuclear accident are radioiodine, radiocaesium and radiostrontium (ICRP 30, 1979). Of the other significant anthropogenic radionuclides likely to be released in most accidents, only small proportions of that ingested will be absorbed in an animals gut, and the main animal products, milk and meat, will not normally be contaminated to a significant extent. Animal products will mostly be contaminated as a result of ingestion of contaminated feed and possibly, but to a much lesser extent, from inhalation (for radioiodine only). Direct external contamination of animals is of little or no consequence in human food production. Radioiodine and radiostrontium are important with respect to contamination of milk; radiocaesium contaminates both milk and meat. The physical and chemical form of a radionuclide can influence its absorption in the animal gut. For example, following the Chernobyl accident radiocaesium incorporated into vegetation by root uptake was more readily absorbed than that associated with the original deposit. The transfer of radiocaesium and radiostrontium to animals will be presented both as transfer coefficients and aggregated transfer coefficients. For most animal meat products, only radiocaesium is important as other radionuclides do not significantly contaminate muscle. Farm animal products are the most important foodstuff determining radiocaesium intake by the average consumer in the Nordic countries. The major potential source of radioiodine and radiostrontium to humans is milk and milk products. Of the different species, the smaller animals have the highest transfer of radiocaesium from fodder to meat and milk. (EG). 68 refs.

  3. Subchronic oral toxicity studies with y-cyclodextrin in rats

    NARCIS (Netherlands)

    Lina, B.A.R.; Bär, A.

    1998-01-01

    The toxicity of γ-cyclodextrin (γ-CD), a cyclic polymer of eight α-1,4-linked glucopyranosyl units with potential applications as a food ingredient, was examined in a 2-week pilot study followed by a 13-week oral toxicity study in Wistar rats. In the 2-week study, the test substance was administered

  4. Larvicidal activity of the water extract of Moringa oleifera seeds against Aedes aegypti and its toxicity upon laboratory animals.

    Science.gov (United States)

    Ferreira, Paulo M P; Carvalho, Ana F U; Farias, Davi F; Cariolano, Nara G; Melo, Vânia M M; Queiroz, Maria G R; Martins, Alice M C; Machado-Neto, Joaquim G

    2009-06-01

    In this work, biological effects of the water extract of Moringa oleifera seeds (WEMOS) were assessed on eggs and 3rd instar larvae of Aedes aegypti and on its toxicity upon laboratory animals (Daphnia magna, mice and rats). Crude WEMOS showed a LC50 value of 1260microg/mL, causing 99.2 +/- 2.9% larvae mortality within 24 h at 5200microg/mL, though this larvicidal activity has been lost completely at 80 masculineC/10 min. WEMOS did not demonstrate capacity to prevent egg hatching. After extensive dialyses of the crude WEMOS into watersoluble dialyzable (DF) and nondyalizable (NDF) fractions, only DF maintained its efficacy to kill larvae. Acute toxicity evaluations on daphnids (EC50 of 188.7microg/mL) and mice (LD50 of 446.5 mg/kg body weight) pointed out to low toxicity. Despite the thymus hypertrophy, WEMOS revealed to be harmless in orally and subacutelytreated rats. In conclusion, WEMOS has thermostable bioactive compounds against Ae. aegypti larvae with apparent molecular mass lower than 12 kDa and moderately toxic potential.

  5. Strengths and limitations of using repeat-dose toxicity studies to predict effects on fertility.

    Science.gov (United States)

    Dent, M P

    2007-08-01

    The upcoming European chemicals legislation REACH (Registration, Evaluation, and Authorisation of Chemicals) will require the risk assessment of many thousands of chemicals. It is therefore necessary to develop intelligent testing strategies to ensure that chemicals of concern are identified whilst minimising the testing of chemicals using animals. Xenobiotics may perturb the reproductive cycle, and for this reason several reproductive studies are recommended under REACH. One of the endpoints assessed in this battery of tests is mating performance and fertility. Animal tests that address this endpoint use a relatively large number of animals and are also costly in terms of resource, time, and money. If it can be shown that data from non-reproductive studies such as in-vitro or repeat-dose toxicity tests are capable of generating reliable alerts for effects on fertility then some animal testing may be avoided. Available rat sub-chronic and fertility data for 44 chemicals that have been classified by the European Union as toxic to fertility were therefore analysed for concordance of effects. Because it was considered appropriate to read across data for some chemicals these data sets were considered relevant for 73 of the 102 chemicals currently classified as toxic to reproduction (fertility) under this system. For all but 5 of these chemicals it was considered that a well-performed sub-chronic toxicity study would have detected pathology in the male, and in some cases, the female reproductive tract. Three showed evidence of direct interaction with oestrogen or androgen receptors (linuron, nonylphenol, and fenarimol). The remaining chemicals (quinomethionate and azafenidin) act by modes of action that do not require direct interaction with steroid receptors. However, both these materials caused in-utero deaths in pre-natal developmental toxicity studies, and the relatively low NOAELs and the nature of the hazard identified in the sub-chronic tests provides an alert

  6. Animal alternatives for whole effluent toxicity testing: Perspectives from a global workshop

    Science.gov (United States)

    Since the 1940’s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that ...

  7. Animal alternatives for whole effluent toxicity testing: Perspectives from a global workshop (presentation)

    Science.gov (United States)

    Since the 1940s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that toxicit...

  8. Animal alternatives for whole effluent toxicity testing: Perspectives from a global workshop

    Science.gov (United States)

    Since the 1940’s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that ...

  9. Animal alternatives for whole effluent toxicity testing: Perspectives from a global workshop (presentation)

    Science.gov (United States)

    Since the 1940s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that toxicit...

  10. Drinking water toxicity study of the environmental contaminant--Bromate.

    Science.gov (United States)

    Dongmei, Liu; Zhiwei, Wang; Qi, Zhu; Fuyi, Cui; Yujuan, Shan; Xiaodong, Liu

    2015-12-01

    Bromate is a byproduct of water disinfection that is produced when waters contain bromide treated with ozone. To investigate the level of the toxicity of bromate and find the most sensitive indicators in a short time, a series of toxicological assessments were conducted including the acute toxicity, cumulative toxicity, genetic toxicity and subacute toxicity of bromate (using Potassium Bromate to represent bromate). The LD50 of orally administered Potassium Bromate was 215 mg/kg in Wistar rats and 464 mg/kg in ICR mice. The cumulative toxicity of Potassium Bromate was not obvious. The Ames test, mouse bone marrow cell micronucleus test and mouse sperm abnormality test did not indicate mutagenicity. The results of the subacute study did not exhibit significant differences in most of the parameters, except the white blood cell count, which was significantly decreased in male rats. In addition, Potassium Bromate influenced the albumin, creatinine, total cholesterol, triglycerides and glucose levels in male rats to various extents. A thorough analysis of the above tests clearly demonstrates that bromate has toxicity, not obvious cumulative toxicity and the white blood cell count can be used as an indicator to reflect the toxicity of bromate and investigate bromate's toxic mechanism.

  11. Estimation of acute oral toxicity using the No Observed Adverse Effect Level (NOAEL) from the 28 day repeated dose toxicity studies in rats.

    Science.gov (United States)

    Bulgheroni, Anna; Kinsner-Ovaskainen, Agnieszka; Hoffmann, Sebastian; Hartung, Thomas; Prieto, Pilar

    2009-02-01

    Acute systemic toxicity is one of the areas of particular concern due to the 2009 deadline set by the 7th Amendment of the Cosmetics Directive (76/768/EEC), which introduces a testing and marketing ban of cosmetic products with ingredients tested on animals. The scientific community is putting considerable effort into developing and validating non-animal alternatives in this area. However, it is unlikely that validated and regulatory accepted alternative methods and/or strategies will be available in March 2009. Following the initiatives undertaken in the pharmaceutical industry to waive the acute oral toxicity testing before going to clinical studies by using information from other in vivo studies, we proposed an approach to identify non-toxic compounds (LD50>2000mg/kg) using information from 28 days repeated dose toxicity studies. Taking into account the high prevalence of non-toxic substances (87%) in the New Chemicals Database, it was possible to set a NOAEL threshold of 200mg/kg that allowed the correct identification of 63% of non-toxic compounds, while testing of cosmetic ingredients.

  12. STRESS RESPONSE STUDIES USING ANIMAL MODELS

    Science.gov (United States)

    This presentation will provide the evidence that ozone exposure in animal models induce neuroendocrine stress response and this stress response modulates lung injury and inflammation through adrenergic and glucocorticoid receptors.

  13. Histopathological study into side-effect toxicity of some drugs used in treatment of cancer.

    Science.gov (United States)

    el-Shazly, M O; Afify, M M; el-Dieb, M K

    1989-03-01

    The effect of cis-chlorodiamine platinum (cisplatin) on different tissues of rat was studied. Nephrotoxicity and neurotoxicity were clearly observed both clinically and histologically. The minimising action of penicillamine as a chelating agent and/or lasix as a diuretic on the toxic side-effect of cisplatin was also studied. Both agents succeeded in reducing the toxic side-effect of cisplatin to some extent but failed to reduce mortality among the experimental animals. The study has also manifested liver and heart to be additional organs susceptible to damage, following cisplatin treatment.

  14. Bias During the Evaluation of Animal Studies?

    OpenAIRE

    Andrew Knight

    2012-01-01

    Simple Summary Animal experimentation evokes strong emotional responses in people on both sides of the debate surrounding its ethical status. However, the true level of its usefulness to society may only be discerned by careful examination of reliable scientific evidence. My recent book, The Costs and Benefits of Animal Experiments, reviewed more than 500 relevant scientific publications. Recently in this journal, however, a reviewer essentially accused me of bias. Yet the conclusions of my b...

  15. [Progress in studies of the male reproductive toxicity of pyrethroid insecticides].

    Science.gov (United States)

    Yao, Ke-Wen; Wang, Jie-Dong

    2008-03-01

    As a new type of pesticides and because of their high performance and low toxicity, pyrethroid insecticides are widely used in place of organochlorine insecticides both in agriculture and in the home. In the recent years, more and more evidence indicates that pyrethroid insecticides can reduce sperm count and motility, cause deformity of the sperm head, increase the count of abnormal sperm, damage sperm DNA and induce its aneuploidy rate, as well as affect sex hormone levels and produce reproductive toxicity. The present article reviews the advances in the studies of male reproductive toxicity of pyrethroid pesticides by experiment in animals and human population, discusses the mechanism of male reproductive toxicity of pesticides and raises some problems concerning the evaluation of human reproductive hazards.

  16. In vivo toxicity studies of fusarium mycotoxins in the last decade: a review.

    Science.gov (United States)

    Escrivá, L; Font, G; Manyes, L

    2015-04-01

    This review summarizes the information regarding the in vivo studies of Fusarium mycotoxins in the last decade. The most common studies are classified as subacute toxicity, subchronic toxicity, acute toxicity, toxicokinetic studies and teratogenicity in order of importance. The most used animals in in vivo studies are pigs, rats, chickens and mice. Fumonisin B1, deoxynivalenol, zearalenone, nivalenol and T-2 toxin are the most studied fusarotoxins. Studies with combinations of mycotoxins are also frequent, deoxynivalenol generally being one of them. The predominant route of administration is oral, administered mostly in the form of naturally contaminated feed. Other administration routes also used are intraperitoneal, intravenous and subcutaneous. In vivo research on Fusarium mycotoxins has increased since 2010 highlighting the need for such studies in the field of food and feed safety.

  17. Flavorings Boost Toxicity of E-Cigarettes in Lab Study

    Science.gov (United States)

    ... news/fullstory_161111.html Flavorings Boost Toxicity of E-Cigarettes in Lab Study Increasing device's voltage, to get ... Sept. 22, 2016 (HealthDay News) -- Flavorings used in e-cigarettes can increase the toxicity of the vapor that ...

  18. One Health and the Environment: Toxic Cyanobacteria, a Case Study

    Science.gov (United States)

    The study of environmental health typically focuses on human populations. However, companion animals, livestock and wildlife also experience adverse health effects from environmental pollutants. Animals may experience direct exposure to pollutants in ambient exposure situations. ...

  19. One Health and the Environment: Toxic Cyanobacteria A Case Study

    Science.gov (United States)

    The study of environmental health typically focuses on human populations. However, companion animals, livestock and wildlife also experience adverse health effects from environmental pollutants. Animals may experience direct exposure to pollutants unlike people in most ambient ex...

  20. DNA-Based Vaccine Protects Against Zika in Animal Study

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_161959.html DNA-Based Vaccine Protects Against Zika in Animal Study ... In animals infected with Zika virus, the synthetic DNA-based vaccine was 100 percent effective in protecting ...

  1. Students' Ideas about Animals: Results from a National Study.

    Science.gov (United States)

    Barman, Charles R.; Barman, Natalie S.; Cox, Mary Lou; Newhouse, Kay Berglund; Goldston, M. Jenice

    2000-01-01

    Explains a study that assesses students' ideas about animals. Evaluates textbooks and trade books according to the identifications and words they use. Discusses student responses from different grade levels on the classification of animals and identifying what is an animal. Summarizes the results of the study and makes recommendations on the…

  2. Animals

    Institute of Scientific and Technical Information of China (English)

    杨光

    2000-01-01

    The largest animal ever to live on the earth is the blue whale(蓝鲸)It weighs about 80 tons--more than 24 elephants. It is more than 30 metres long. A newborn baby whale weighs as much as a big elephant.

  3. Multiple mitigation mechanisms: Effects of submerged plants on the toxicity of nine insecticides to aquatic animals.

    Science.gov (United States)

    Brogan, William R; Relyea, Rick A

    2017-01-01

    Understanding the processes that regulate contaminant impacts in nature is an increasingly important challenge. For insecticides in surface waters, the ability of aquatic plants to sorb, or bind, hydrophobic compounds has been identified as a primary mechanism by which toxicity can be mitigated (i.e. the sorption-based model). However, recent research shows that submerged plants can also rapidly mitigate the toxicity of the less hydrophobic insecticide malathion via alkaline hydrolysis (i.e. the hydrolysis-based model) driven by increased water pH resulting from photosynthesis. However, it is still unknown how generalizable these mitigation mechanisms are across the wide variety of insecticides applied today, and whether any general rules can be ascertained about which types of chemicals may be mitigated by each mechanism. We quantified the degree to which the submerged plant Elodea canadensis mitigated acute (48-h) toxicity to Daphnia magna using nine commonly applied insecticides spanning three chemical classes (carbamates: aldicarb, carbaryl, carbofuran; organophosphates: malathion, diazinon, chlorpyrifos; pyrethroids: permethrin, bifenthrin, lambda-cyhalothrin). We found that insecticides possessing either high octanol-water partition coefficients (log Kow) values (i.e. pyrethroids) or high susceptibility to alkaline hydrolysis (i.e. carbamates and malathion) were all mitigated to some degree by E. canadensis, while the plant had no effect on insecticides possessing intermediate log Kow values and low susceptibility to hydrolysis (i.e. chlorpyrifos and diazinon). Our results provide the first general insights into which types of insecticides are likely to be mitigated by different mechanisms based on known chemical properties. We suggest that current models and mitigation strategies would be improved by the consideration of both mitigation models. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Duration of Acute and Chronic Toxicity Testing in Animals (ICH S4A and S4B)

    DEFF Research Database (Denmark)

    Spindler, Per; Van Cauteren, Herman

    2013-01-01

    for the ICH S4B guideline regarding the duration of non-rodent repeated dose toxicity studies is explained and lessons learned are discussed. Since the guideline was issued in 1997 changes occurred in e.g. the language of the European legislation, and the requirements for non-clinical studies to support...

  5. Studies on Oxygen Toxicity in the Lungs.

    Science.gov (United States)

    1980-02-29

    a mean of 7.6. The increased labeled the shaded area the standard deviation of the mean of control animalL cells were in groups scattered throughout...0 and D art statistically similar. -27- 355 HACKNEY Er AL. WEIGHT CHANGE VS DAYS ..................................................... . .. -3- -.4

  6. Acrylamide: inhibition of formation in processed food and mitigation of toxicity in cells, animals, and humans.

    Science.gov (United States)

    Friedman, Mendel

    2015-06-01

    Potentially toxic acrylamide is largely derived from the heat-inducing reactions between the amino group of the amino acid asparagine and carbonyl groups of glucose and fructose in plant-derived foods including cereals, coffees, almonds, olives, potatoes, and sweet potatoes. This review surveys and consolidates the following dietary aspects of acrylamide: distribution in food, exposure and consumption by diverse populations, reduction of the content in different food categories, and mitigation of adverse in vivo effects. Methods to reduce acrylamide levels include selecting commercial food with a low acrylamide content, selecting cereal and potato varieties with low levels of asparagine and reducing sugars, selecting processing conditions that minimize acrylamide formation, adding food-compatible compounds and plant extracts to food formulations before processing that inhibit acrylamide formation during processing of cereal products, coffees, teas, olives, almonds, and potato products, and reducing multiorgan toxicity (antifertility, carcinogenicity, neurotoxicity, teratogenicity). The herein described observations and recommendations are of scientific interest for food chemistry, pharmacology, and toxicology, but also have the potential to benefit nutrition, food safety, and human health.

  7. Inactivation of Ricin Toxin by Nanosecond Pulsed Electric Fields Including Evidences from Cell and Animal Toxicity

    Science.gov (United States)

    Wei, Kai; Li, Wei; Gao, Shan; Ji, Bin; Zang, Yating; Su, Bo; Wang, Kaile; Yao, Maosheng; Zhang, Jue; Wang, Jinglin

    2016-01-01

    Ricin is one of the most toxic and easily produced plant protein toxin extracted from the castor oil plant, and it has been classified as a chemical warfare agent. Here, nanosecond pulsed electric fields (nsPEFs) at 30 kV/cm (pulse durations: 10 ns, 100 ns, and 300 ns) were applied to inactivating ricin up to 4.2 μg/mL. To investigate the efficacy, cells and mice were tested against the ricin treated by the nsPEFs via direct intraperitoneal injection and inhalation exposure. Results showed that nsPEFs treatments can effectively reduce the toxicity of the ricin. Without the nsPEFs treatment, 100% of mice were killed upon the 4 μg ricin injection on the first day, however 40% of the mice survived the ricin treated by the nsPEFs. Compared to injection, inhalation exposure even with higher ricin dose required longer time to observe mice fatality. Pathological observations revealed damages to heart, lung, kidney, and stomach after the ricin exposure, more pronounced for lung and kidney including severe bleeding. Sodium dodecyl sulfate polyacrylamide gel electrophoresis(SDS-PAGE) and circular dichroism (CD) analyses revealed that although the primary structure of ricin was not altered, its secondary structures (beta-sheet and beta-turn) underwent transition upon the nsPEFs treatment.

  8. Inactivation of Ricin Toxin by Nanosecond Pulsed Electric Fields Including Evidences from Cell and Animal Toxicity.

    Science.gov (United States)

    Wei, Kai; Li, Wei; Gao, Shan; Ji, Bin; Zang, Yating; Su, Bo; Wang, Kaile; Yao, Maosheng; Zhang, Jue; Wang, Jinglin

    2016-01-05

    Ricin is one of the most toxic and easily produced plant protein toxin extracted from the castor oil plant, and it has been classified as a chemical warfare agent. Here, nanosecond pulsed electric fields (nsPEFs) at 30 kV/cm (pulse durations: 10 ns, 100 ns, and 300 ns) were applied to inactivating ricin up to 4.2 μg/mL. To investigate the efficacy, cells and mice were tested against the ricin treated by the nsPEFs via direct intraperitoneal injection and inhalation exposure. Results showed that nsPEFs treatments can effectively reduce the toxicity of the ricin. Without the nsPEFs treatment, 100% of mice were killed upon the 4 μg ricin injection on the first day, however 40% of the mice survived the ricin treated by the nsPEFs. Compared to injection, inhalation exposure even with higher ricin dose required longer time to observe mice fatality. Pathological observations revealed damages to heart, lung, kidney, and stomach after the ricin exposure, more pronounced for lung and kidney including severe bleeding. Sodium dodecyl sulfate polyacrylamide gel electrophoresis(SDS-PAGE) and circular dichroism (CD) analyses revealed that although the primary structure of ricin was not altered, its secondary structures (beta-sheet and beta-turn) underwent transition upon the nsPEFs treatment.

  9. Aluminum in the central nervous system (CNS): toxicity in humans and animals, vaccine adjuvants, and autoimmunity.

    Science.gov (United States)

    Shaw, C A; Tomljenovic, L

    2013-07-01

    We have examined the neurotoxicity of aluminum in humans and animals under various conditions, following different routes of administration, and provide an overview of the various associated disease states. The literature demonstrates clearly negative impacts of aluminum on the nervous system across the age span. In adults, aluminum exposure can lead to apparently age-related neurological deficits resembling Alzheimer's and has been linked to this disease and to the Guamanian variant, ALS-PDC. Similar outcomes have been found in animal models. In addition, injection of aluminum adjuvants in an attempt to model Gulf War syndrome and associated neurological deficits leads to an ALS phenotype in young male mice. In young children, a highly significant correlation exists between the number of pediatric aluminum-adjuvanted vaccines administered and the rate of autism spectrum disorders. Many of the features of aluminum-induced neurotoxicity may arise, in part, from autoimmune reactions, as part of the ASIA syndrome.

  10. ANIMALS

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Mammals(哺乳动物)Mammals are the world's most dominant(最占优势的)animal.They are extremely(非常)diverse(多种多样的)creatures(生物,动物)that include(包括)the biggest ever animal (the blue whale鲸,which eats up to 6 tons every day),the smallest(leaf-nosed bat小蹄蝠) and the laziest(sloth树獭,who spends 80% of their time sleeping).There are over 4,600 kinds of mammals and they live in very different environments(环境)—oceans(海洋),rivers,the jungle(丛林),deserts,and plains(平原).

  11. Toxicity of molybdenum and its trace analysis in animal tissues and plants.

    Science.gov (United States)

    Abbasi, S A

    1981-01-01

    A sensitive, selective, rapid and reproducible method is presented for the analysis of submicrogram levels of molybdenum in animal tissues (Liver) and plants. The method is based on solvent extraction of Molybdenum (VI) using isoamyl alcohol solution of N-o-tolyl-o-methoxy-benzohydroxamic acid at pH 1.5-2.5, and subsequent spectrophotometric determination of the yellow extract at 350 nm.

  12. Studying Biotechnological Methods Using Animations: The Teacher's Role

    Science.gov (United States)

    Yarden, Hagit; Yarden, Anat

    2011-01-01

    Animation has great potential for improving the way people learn. A number of studies in different scientific disciplines have shown that instruction involving computer animations can facilitate the understanding of processes at the molecular level. However, using animation alone does not ensure learning. Students sometimes miss essential features…

  13. Studying Biotechnological Methods Using Animations: The Teacher's Role

    Science.gov (United States)

    Yarden, Hagit; Yarden, Anat

    2011-12-01

    Animation has great potential for improving the way people learn. A number of studies in different scientific disciplines have shown that instruction involving computer animations can facilitate the understanding of processes at the molecular level. However, using animation alone does not ensure learning. Students sometimes miss essential features when they watch only animations, mainly due to the cognitive load involved. Moreover, students seem to attribute a great deal of authority to the computer and may develop misconceptions by taking animations of abstract concepts too literally. In this study, we attempted to explore teachers' perceptions concerning the use of animations in the classroom while studying biotechnological methods, as well as the teachers' contribution to the enactment of animations in class. Thirty high-school biotechnology teachers participated in a professional development workshop, aimed at investigating how teachers plan for and support learning with animation while studying biotechnological methods in class. From that sample, two teachers agreed to participate in two case studies aimed at characterizing teachers' contribution to the enactment of animations in class while studying biotechnological methods. Our findings reveal marked teacher contribution in the following three aspects: establishing the "hands-on" point of view, helping students deal with the cognitive load that accompanies the use of animation, and implementing constructivist aspects of knowledge construction while studying using animations.

  14. Acute and Subchronic Toxicity Study of Euphorbia hirta L. Methanol Extract in Rats

    Directory of Open Access Journals (Sweden)

    Kwan Yuet Ping

    2013-01-01

    Full Text Available Despite Euphorbia hirta L. ethnomedicinal benefits, very few studies have described the potential toxicity. The aim of the present study was to evaluate the in vivo toxicity of methanolic extracts of E. hirta. The acute and subchronic oral toxicity of E. hirta was evaluated in Sprague Dawley rats. The extract at a single dose of 5000 mg/kg did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. Therefore, the LD 50 of this plant was estimated to be more than 5000 mg/kg. In the repeated dose 90-day oral toxicity study, the administration of 50 mg/kg, 250 mg/kg, and 1000 mg/kg/day of E. hirta extract per body weight revealed no significant difference (P>0.05 in food and water consumptions, body weight change, haematological and biochemical parameters, relative organ weights, and gross findings compared to the control group. Macropathology and histopathology examinations of all organs including the liver did not reveal morphological alteration. Analyses of these results with the information of signs, behaviour, and health monitoring could lead to the conclusion that the long-term oral administration of E. hirta extract for 90 days does not cause sub-chronic toxicity.

  15. Acute and subchronic toxicity study of Euphorbia hirta L. methanol extract in rats.

    Science.gov (United States)

    Yuet Ping, Kwan; Darah, Ibrahim; Chen, Yeng; Sreeramanan, Subramaniam; Sasidharan, Sreenivasan

    2013-01-01

    Despite Euphorbia hirta L. ethnomedicinal benefits, very few studies have described the potential toxicity. The aim of the present study was to evaluate the in vivo toxicity of methanolic extracts of E. hirta. The acute and subchronic oral toxicity of E. hirta was evaluated in Sprague Dawley rats. The extract at a single dose of 5,000 mg/kg did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. Therefore, the LD 50 of this plant was estimated to be more than 5,000 mg/kg. In the repeated dose 90-day oral toxicity study, the administration of 50 mg/kg, 250 mg/kg, and 1,000 mg/kg/day of E. hirta extract per body weight revealed no significant difference (P > 0.05) in food and water consumptions, body weight change, haematological and biochemical parameters, relative organ weights, and gross findings compared to the control group. Macropathology and histopathology examinations of all organs including the liver did not reveal morphological alteration. Analyses of these results with the information of signs, behaviour, and health monitoring could lead to the conclusion that the long-term oral administration of E. hirta extract for 90 days does not cause sub-chronic toxicity.

  16. Thirty-day rat toxicity study reveals reversible liver toxicity of mifepristone (RU486) and metapristone.

    Science.gov (United States)

    Xiao, Yingying; Zhu, Yewei; Yu, Suhong; Yan, Cuicui; Ho, Rodney J Y; Liu, Jian; Li, Tao; Wang, Jie; Wan, Liyuan; Yang, Xingtian; Xu, Huo; Wang, Jichuang; Tu, Xiaohuang; Jia, Lee

    2016-01-01

    Mifepristone (RU486) is an oral first-line contraceptive used by hundreds of millions of women, and recently it was tested for anticancer activity in both genders worldwide. We are developing metapristone (the N-monodemethyl RU486) as a potential metastasis chemopreventive. The present acute and 30-d subacute toxicity study aimed at examining and compared in parallel the potential toxicity of the two drugs. The single-dose acute toxicity and 30-d subacute toxicity studies were conducted in mice and rats, respectively, by gavaging metapristone or mifepristone at various doses. Blood samples and organs were collected for blood chemistry, hematology and histology analyses. Oral mifepristone (3000 mg/kg) caused 30% and 40% death in female and male mice, respectively, within 15 h post-dosing. In comparison, the same dose of metapristone produced 30% acute death in males only. Thirty-day oral administration of the two drugs to rats (12.5, 50 and 200 mg/kg/day) caused reversible hepatotoxicity that only occurred at 200 mg/kg/day group, evidenced by the elevated liver enzyme activity and liver organ weight. The present study, for the first time, reveals reversible hepatotoxicity in rats caused by the 30-d consecutive administration at the high dose, and warns the potential hepatotoxicity caused by long-term administrations of high doses of mifepristone or metapristone in clinical trials but not by the acute single abortion doses.

  17. Acute and Short-Term Inhalation Toxicity Study of FT Fuel

    Science.gov (United States)

    2011-02-01

    than JP-8 in equivalent tests . In addition, micronucleus induction was tested ; FT jet fuel does not induce micronuclei, indicating that the fuel is...OECD, 1981). A separate group of rats were used as controls for assessment of micronucleus induction in order to complete the genotoxicity testing of...toxicity study in F344 rats was investigated in a short-term mutagenicity assay, the mammalian erythrocyte micronucleus (MN) test . Animals were exposed

  18. Acute oral toxicity and biodistribution study of zinc-aluminium-levodopa nanocomposite

    Science.gov (United States)

    Kura, Aminu Umar; Saifullah, Bullo; Cheah, Pike-See; Hussein, Mohd Zobir; Azmi, Norazrina; Fakurazi, Sharida

    2015-03-01

    Layered double hydroxide (LDH) is an inorganic-organic nano-layered material that harbours drug between its two-layered sheets, forming a sandwich-like structure. It is attracting a great deal of attention as an alternative drug delivery (nanodelivery) system in the field of pharmacology due to their relative low toxic potential. The production of these nanodelivery systems, aimed at improving human health through decrease toxicity, targeted delivery of the active compound to areas of interest with sustained release ability. In this study, we administered zinc-aluminium-LDH-levodopa nanocomposite (ZAL) and zinc-aluminium nanocomposite (ZA) to Sprague Dawley rats to evaluate for acute oral toxicity following OECD guidelines. The oral administration of ZAL and ZA at a limit dose of 2,000 mg/kg produced neither mortality nor acute toxic signs throughout 14 days of the observation. The percentage of body weight gain of the animals showed no significant difference between control and treatment groups. Animal from the two treated groups gained weight continuously over the study period, which was shown to be significantly higher than the weight at the beginning of the study ( P models for short periods of time. It also highlighted the potential distribution ability of Tween-80 coated nanocomposite after oral administration.

  19. 90-Day Inhalation Toxicity Study of FT Fuel

    Science.gov (United States)

    2011-08-01

    vapors of a distillate of light catalytic cracked naphtha (LCCN-D, CAS no. 64741-55-5) in Sprague-Dawley rats. Target exposure concentrations were 0...cracked naphtha distillate in rats. Int J Toxicol. (2001) 20:307-319. McDougal JN, Rogers JV. Local and systemic toxicity of JP-8 from cutaneous exposures...petroleum blending streams: inhalation subchronic toxicity/neurotoxicity study of a light catalytic reformed naphtha distillate in rats. J Toxicol

  20. Neurotoxicity of 1-bromopropane: Evidence from animal experiments and human studies

    Directory of Open Access Journals (Sweden)

    Gaku Ichihara

    2012-04-01

    Full Text Available 1-Bromopropane was introduced as an alternative to ozone layer-depleting solvents such as chlorofluorocarbons and 1,1,1-trichloroethane. However, a dozen human cases have been reported with symptoms and signs of toxicity to 1-bromopropane including numbness, diminished vibration sense in the lower extremities as well as ataxic gait. An epidemiological study also demonstrated dose-dependent prolongation of distal latency and decrease in vibration sense in the lower extremities. The initial animal experiments helped to identify and analyze the initial human case of 1-bromopropane toxicity. However, animal data that can explain the central nervous system disorders in humans are limited. Nonetheless, animal data should be carefully interpreted especially in a high-order function of the central nervous system or neurological signs such as ataxia that is influenced by fundamental anatomical/physiological differences between humans and animals. Enzymatic activity in the liver may explain partly the difference in the susceptibility between humans and animals, but further studies are needed to clarify the biological factors that can explain the difference and commonality among the species.

  1. The fish embryo toxicity test as an animal alternative method in hazard and risk assessment and scientific research

    Energy Technology Data Exchange (ETDEWEB)

    Embry, Michelle R., E-mail: membry@ilsi.org [ILSI Health and Environmental Sciences Institute, 1156 15th Street, NW, Suite 200, Washington, DC 20005 (United States); Belanger, Scott E., E-mail: belanger.se@pg.com [Procter and Gamble, Central Product Safety, PO Box 538707, Miami Valley Innovation Center, Cincinnati, OH 45253-8707 (United States); Braunbeck, Thomas A., E-mail: braunbeck@zoo.uni-heidelberg.de [University of Heidelberg, Im Neuenheimer Feld 230, Heidelberg D -69120 (Germany); Galay-Burgos, Malyka, E-mail: malyka.galay-burgos@ecetoc.org [European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC), 4 Avenue E. Van Nieuwenhuyse B-1160, Brussels (Belgium); Halder, Marlies, E-mail: marlies.halder@jrc.ec.europa.eu [European Commission, Joint Research Centre, Institute for Health and Consumer Protection, In-Vitro Methods Unit TP-580 Ispra 21027 (Italy); Hinton, David E., E-mail: dhinton@duke.edu [Duke University, Nicholas School of the Environment, PO Box 90328, Durham, NC 27708, Unites States (United States); Leonard, Marc A., E-mail: mleonard@rd.loreal.com [L' Oreal Recherche Avancee, Unite d' Ecotoxicologie, 1 av. E. Schueller, 93601 Aulnay sous bois (France); Lillicrap, Adam, E-mail: Adam.lillicrap@niva.no [AstraZeneca, Freshwater Quarry, Brixham TQ5 8BA (United Kingdom); Norberg-King, Teresa, E-mail: norberg-king.teresa@epa.gov [U.S. EPA, Mid-Continent Ecology Division, 6201 Congdon Boulevard, Duluth, MN 55804-1636 (United States); Whale, Graham, E-mail: graham.whale@shell.com [Shell Global Solutions, Analytical Technology, P.O. Box 1, Chester CH1 3SH (United Kingdom)

    2010-04-15

    Animal alternatives research has historically focused on human safety assessments and has only recently been extended to environmental testing. This is particularly for those assays that involve the use of fish. A number of alternatives are being pursued by the scientific community including the fish embryo toxicity (FET) test, a proposed replacement alternative to the acute fish test. Discussion of the FET methodology and its application in environmental assessments on a global level was needed. With this emerging issue in mind, the ILSI Health and Environmental Sciences Institute (HESI) and the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) held an International Workshop on the Application of the Fish Embryo Test as an Animal Alternative Method in Hazard and Risk Assessment and Scientific Research in March, 2008. The workshop included approximately 40 scientists and regulators representing government, industry, academia, and non-governmental organizations from North America, Europe, and Asia. The goal was to review the state of the science regarding the investigation of fish embryonic tests, pain and distress in fish, emerging approaches utilizing fish embryos, and the use of fish embryo toxicity test data in various types of environmental assessments (e.g., hazard, risk, effluent, and classification and labeling of chemicals). Some specific key outcomes included agreement that risk assessors need fish data for decision-making, that extending the FET to include eluethereombryos was desirable, that relevant endpoints are being used, and that additional endpoints could facilitate additional uses beyond acute toxicity testing. The FET was, however, not yet considered validated sensu OECD. An important action step will be to provide guidance on how all fish tests can be used to assess chemical hazard and to harmonize the diverse terminology used in test guidelines adopted over the past decades. Use of the FET in context of effluent assessments

  2. The fish embryo toxicity test as an animal alternative method in hazard and risk assessment and scientific research.

    Science.gov (United States)

    Embry, Michelle R; Belanger, Scott E; Braunbeck, Thomas A; Galay-Burgos, Malyka; Halder, Marlies; Hinton, David E; Léonard, Marc A; Lillicrap, Adam; Norberg-King, Teresa; Whale, Graham

    2010-04-15

    Animal alternatives research has historically focused on human safety assessments and has only recently been extended to environmental testing. This is particularly for those assays that involve the use of fish. A number of alternatives are being pursued by the scientific community including the fish embryo toxicity (FET) test, a proposed replacement alternative to the acute fish test. Discussion of the FET methodology and its application in environmental assessments on a global level was needed. With this emerging issue in mind, the ILSI Health and Environmental Sciences Institute (HESI) and the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) held an International Workshop on the Application of the Fish Embryo Test as an Animal Alternative Method in Hazard and Risk Assessment and Scientific Research in March, 2008. The workshop included approximately 40 scientists and regulators representing government, industry, academia, and non-governmental organizations from North America, Europe, and Asia. The goal was to review the state of the science regarding the investigation of fish embryonic tests, pain and distress in fish, emerging approaches utilizing fish embryos, and the use of fish embryo toxicity test data in various types of environmental assessments (e.g., hazard, risk, effluent, and classification and labeling of chemicals). Some specific key outcomes included agreement that risk assessors need fish data for decision-making, that extending the FET to include eluethereombryos was desirable, that relevant endpoints are being used, and that additional endpoints could facilitate additional uses beyond acute toxicity testing. The FET was, however, not yet considered validated sensu OECD. An important action step will be to provide guidance on how all fish tests can be used to assess chemical hazard and to harmonize the diverse terminology used in test guidelines adopted over the past decades. Use of the FET in context of effluent assessments

  3. Acute and 28-day subchronic toxicity studies of mangiferin, a glucosylxanthone isolated from Mangifera indica L. stem bark.

    Directory of Open Access Journals (Sweden)

    Yalena Prado

    2015-02-01

    Full Text Available Context: Pharmacological properties of mangiferin have been reported, but few studies have investigated mangiferin toxicity. Aims: To study the acute and 28-day toxicity effects of mangiferin in rodents. Methods: Single doses of mangiferin were administered by oral or i.p. route or were applied dermally to Sprague-Dawley rats and Balb/C mice. Clinical symptoms of animals were observed during 14 days after treatment. Animals also received single oral doses daily for 28 consecutive days. Blood biochemistry, hematology and pathology findings were reported. Results: In the acute study, no toxic effects were observed after dermal exposure to mangiferin 2000 mg/kg but transient dyspnea, flank position and piloerection were observed after oral administration to this xanthone. I.p. administration induced similar toxicity signs, but at the highest dose (2000 mg/kg all mice, one female rat and one male rat died. Rats orally treated with mangiferin (250-1000 mg/kg for 28 days did not show any abnormal clinical signs or hematology alterations, when compared to control group animals. Histopathological alterations like vacuolar degeneration, necrosis and increment of apoptosis of the acinar cells were observed in the exocrine pancreas of rats at 1000 mg/kg. This suggesting that exocrine pancreas was the target organ for mangiferin’s toxicity. Conclusions: These studies indicated that acute and subchronic toxicities of mangiferin for oral exposure are low.

  4. Importance of genomic studies for drug withdrawal with mental toxicities

    Directory of Open Access Journals (Sweden)

    Da Yong Lu

    2011-09-01

    Full Text Available Undesired side-effects and toxicities of drugs, especially in the area of new-drug development, are negligibleless, unpredicable and often disastrous once being encountered. The suicidal behavior caused by antidepressant treatment is a typical of clinical evidence recently being discovered. We previously hypothesized that patients’ genetic status would decide the suicidal incident rate of antidepressants - it is pharmacogenetics of antidepressants may contribute of this toxicity in patients. In this review, we discuss this problem by comparing many strings of pharmacogenomics evidence of antidepressants recently being published with many other strings of evidence such as drug withdrawal with hepatotoxicity. We argue herein that pharmacogenetics may be very useful in drug withdrawal for mental toxicity. Because this is low-incidence toxicities, which are more reliable on human’s genetic characteristics. We stress the importance of genomics studies for drug withdrawal in future.

  5. [A retrospective study of animal poisoning reports to the Swiss Toxicological Information Centre (1997 - 2006)].

    Science.gov (United States)

    Curti, R; Kupper, J; Kupferschmidt, H; Naegeli, H

    2009-06-01

    The purpose of this retrospective study was to analyse the etiology, frequency and outcome of toxicological cases recorded by the consultation service of the Swiss Toxicological Information Centre (STIC) hotline over a 10-year period, from 1997 to 2006. A detailed analysis of this database indicates that common human drugs not intended for use in animals, as well as pesticides and toxic plants represent the most prominent hazards involved in the reported cases of animal poisonings. The comparison with a previous survey from the years 1976 - 1985 revealed new toxic risks due to the accidental uptake of cannabis products, castor seeds or chocolate by dogs. In addition, there is a striking increase of serious poisonings with pyrethroids in cats. The follow-up reports delivered by veterinarians also reflect novel pharmacological and technological trends in the management of poisonings.

  6. Toxicity Reference Database

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Toxicity Reference Database (ToxRefDB) contains approximately 30 years and $2 billion worth of animal studies. ToxRefDB allows scientists and the interested...

  7. Studies on Toxicity, Anti_stress and Hepato_protective Properties of Kombucha Tea

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective The objective of the study was to evaluate toxicity, anti_stress activity and hepato_protective properties of Kombucha tea. Method Kombucha tea was fed orally for 15 days using three different doses i.e. normal dose, five and ten times the dose. Rats were then sacrificed and various biochemical, and histological parameters were estimated. Anti_stress activity was evaluated either by 1) by exposing animals to cold and hypoxia and estimating the levels of malondialdehyde and reduced glutathione in plasma/ blood or 2) by subjecting the animals to restraint stress and recording faecal output. Hepato_toxicity was induced by challenging the animals to an acute dose of paracetamol (1 gm/kg) orally and determining the plasma levels of SGPT, SGOT and MDA. Results The effect of oral administration of different doses of K_tea to albino rats was examined and the results indicate that K_tea has no significant toxicity as revealed by various biochemical and histopathological parameters. K_tea has been found to prevent lipid peroxidation and fall in reduced glutathione level when rats were exposed to cold and hypoxia in simulated chamber. Further, K_tea has also been found to decrease the Wrap_restraint faecal pellet output in rats. K_tea has also been found to decrease paracetamol induced hepatotoxicity significantly. Conclusion The study shows that K_tea has anti_stress and hepato_protective activities.

  8. Studies on Toxicity,Anti—stress and Hepato—Protective properties of Kombucha Tea

    Institute of Scientific and Technical Information of China (English)

    PAULINE,T.; KAVIMANI,S

    2001-01-01

    Objective :The objective of the study was to evaluate toxicity,anti-stress activity and hepatoprotective properties of Kombucha tea.Method :Kombucha tea was fed orally for 15 days using three different doses i.e.normal dose,five and ten times the dose,Rats were then sacrficed and various biochemical,and histological parameters were estimated.Anti-stress activity was evaluated either by 1)by exposing animals to cold and hypoxia and estimating the levels of malondialdehyde and reduced glutathione in plasma/blood or 2) by subjecting the animals to restraint stress and recording faecal output.Hepato-toxicity was induced by challenging the animals to an acute dose of paracetamol(1gm/kg)orally and determining the plasma levels of SGPT,SGOT and MDA.REsults:The effect of oral administration of different doses of K-tea to albion rats was examined and the results indicate that K-tea has no significant toxicity as revealed by various biochemical and histopathological parameters.K-tea has been found to prevent lipid peroxidation and fall in reduced glutathione level when rats were exposed to cold and hypoxia in simulated chamber.Further,K-tea has also been found to decrease the Wrap-restraint faecal pellet output in rats.K-tea has also been found to decrease paracetamol induced hepatotoxicity significantly.Conclusion:The study shows that K-tea has anti-stress and hepato-protective activities.

  9. Animal models to study gluten sensitivity.

    Science.gov (United States)

    Marietta, Eric V; Murray, Joseph A

    2012-07-01

    The initial development and maintenance of tolerance to dietary antigens is a complex process that, when prevented or interrupted, can lead to human disease. Understanding the mechanisms by which tolerance to specific dietary antigens is attained and maintained is crucial to our understanding of the pathogenesis of diseases related to intolerance of specific dietary antigens. Two diseases that are the result of intolerance to a dietary antigen are celiac disease (CD) and dermatitis herpetiformis (DH). Both of these diseases are dependent upon the ingestion of gluten (the protein fraction of wheat, rye, and barley) and manifest in the gastrointestinal tract and skin, respectively. These gluten-sensitive diseases are two examples of how devastating abnormal immune responses to a ubiquitous food can be. The well-recognized risk genotype for both is conferred by either of the HLA class II molecules DQ2 or DQ8. However, only a minority of individuals who carry these molecules will develop either disease. Also of interest is that the age at diagnosis can range from infancy to 70-80 years of age. This would indicate that intolerance to gluten may potentially be the result of two different phenomena. The first would be that, for various reasons, tolerance to gluten never developed in certain individuals, but that for other individuals, prior tolerance to gluten was lost at some point after childhood. Of recent interest is the concept of non-celiac gluten sensitivity, which manifests as chronic digestive or neurologic symptoms due to gluten, but through mechanisms that remain to be elucidated. This review will address how animal models of gluten-sensitive disorders have substantially contributed to a better understanding of how gluten intolerance can arise and cause disease.

  10. Animal Models to Study Gluten Sensitivity1

    Science.gov (United States)

    Marietta, Eric V.; Murray, Joseph A.

    2012-01-01

    The initial development and maintenance of tolerance to dietary antigens is a complex process that, when prevented or interrupted, can lead to human disease. Understanding the mechanisms by which tolerance to specific dietary antigens is attained and maintained is crucial to our understanding of the pathogenesis of diseases related to intolerance of specific dietary antigens. Two diseases that are the result of intolerance to a dietary antigen are celiac disease (CD) and dermatitis herpetiformis (DH). Both of these diseases are dependent upon the ingestion of gluten (the protein fraction of wheat, rye, and barley) and manifest in the gastrointestinal tract and skin, respectively. These gluten-sensitive diseases are two examples of how devastating abnormal immune responses to a ubiquitous food can be. The well-recognized risk genotype for both is conferred by either of the HLA class II molecules DQ2 or DQ8. However, only a minority of individuals who carry these molecules will develop either disease. Also of interest is that the age at diagnosis can range from infancy to 70–80 years of age. This would indicate that intolerance to gluten may potentially be the result of two different phenomena. The first would be that, for various reasons, tolerance to gluten never developed in certain individuals, but that for other individuals, prior tolerance to gluten was lost at some point after childhood. Of recent interest is the concept of non-celiac gluten sensitivity, which manifests as chronic digestive or neurologic symptoms due to gluten, but through mechanisms that remain to be elucidated. This review will address how animal models of gluten-sensitive disorders have substantially contributed to a better understanding of how gluten intolerance can arise and cause disease. PMID:22572887

  11. ACUTE ORAL TOXICITY STUDY OF CLINACANTHUS NUTANS IN MICE

    Directory of Open Access Journals (Sweden)

    Xiu Wen P'ng, Gabriel Akyirem Akowuah and Jin Han Chin*

    2012-11-01

    Full Text Available Clinacanthus nutans Lindau (Family: Acanthaceae has attracted public interest recently due to its high medicinal values for the treatment of cancer, inflammation and various skin problems. This study was aimed to determine the oral LD50 value of the methanol leaves extract of C. nutans and identify the targeted organs in mice. This acute oral toxicity study was conducted in accordance to OECD 423 guidelines by using male Swiss albino mice weighing 25-35 g. First group was served as control group which received distilled water (vehicle while second and third group were orally treated with single daily dose of 0.9 g/kg and 1.8 g/kg of methanol leaves extract of C. nutans, respectively. All the animals were closely observed for 14 days. Body weight for each mouse was recorded at day-0, day-3, day-7 and day-14. Relative organ weights for liver, kidney, spleen, lung and heart were also determined. All the results were presented as mean ± standard deviation and analyzed using Dunnett’s Test after ANOVA test. From the results obtained, no mortality was observed in both treatment groups either post 24 hours or 14 days of oral administration of C. nutans. Body weight for each mouse and relative organ weight showed insignificant difference when compared to the control group. In conclusion, acute exposure of 1.8 g/kg of C. nutans was safe in male mice without causing any adverse effects or mortality. The oral LD50 of methanol leaves extract of C. nutans was suggested to be greater than 1.8 g/kg bw in male mice.

  12. Neurological effects of white spirit: Contribution of animal studies during a 30-year period

    DEFF Research Database (Denmark)

    Nielsen, Gunnar Damgård; Lund, Søren Peter; Ladefoged, Ole

    2006-01-01

    , but the neurophysiological tests showed adverse effects at this level. Fourth, neurophysiological methods may be more sensitive than histopathological, neurobehavioural and neurochemical methods. Overall, white spirit with a high and a low content of aromatics showed no overt difference in long-term effects in animals......Numerous studies have suggested that long-term occupational exposure to white spirit may cause chronic toxic encephalopathy (WHO 1996). This review summarizes the chronic nervous system effects of white spirit in animal studies during a 30-year period. First, routine histopathology was consistently...... unable to reveal adverse peripheral or central nervous system effects after inhalation of white spirit. Second, neurobehavioural studies in animals showed no adverse effect after inhalation of white spirit with a high content of aromatics in contrast to what was found with products with a low content...

  13. Preparation, characterization and related in vivo release, safety and toxicity studies of long acting lanreotide microspheres.

    Science.gov (United States)

    Wang, Shuang; Wu, Mingsheng; Li, Dan; Jiao, Mingli; Wang, Lan; Zhang, Haifeng; Liu, Huaiyu; Wang, Daifeng; Han, Bing

    2012-01-01

    The goal of this project was to prepare long-acting lanreotide acetate poly(lactic-co-glycolic acid) (PLGA) microspheres and to analyze the in vivo and in vitro release, safety and toxicology of these preparations. Long-acting lanreotide acetate PLGA microspheres that exhibited a 5-week slow-release period were prepared by a multiple-emulsion solvent evaporation method. Physical characterization, as well as the analysis of the in vivo and in vitro release, safety, acute toxicity and chronic toxicity of the lanreotide microspheres, were conducted in animal models in rats, guinea pigs, rabbits and beagle dogs. The lanreotide acetate PLGA microspheres prepared by multiple-emulsion solvent evaporation had smooth surfaces, uniform particle size and stable lanreotide loading. In vivo and in vitro experiments showed that the lanreotide acetate PLGA microspheres could continuously release lanreotide for 5 weeks. The safety of these long acting lanreotide microspheres was good in the following animal models: active systemic anaphylaxis test in guinea pigs, passive cutaneous anaphylaxis test in rats, hemolytic test in rabbits, local skin irritation test after subcutaneous administration in rabbits and muscle stimulation test in rabbits. Furthermore, no significant acute toxicity or chronic toxicity was observed after administration of lanreotide acetate PLGA microspheres in beagle dogs at dosages up to 22 mg/kg. The lanreotide acetate PLGA microspheres that were prepared in this study exhibited beneficial characteristics in apparent property and structural stability, as well as in release trends in vivo and in vitro.

  14. Toxicity of novel anti-hepatitis drug bicyclol: A preclinical study

    Institute of Scientific and Technical Information of China (English)

    Geng-Tao Liu; Yan Li; Huai-Ling Wei; Hong Lu; Hui Zhang; Yu-Gui Gao; Ling-Zhi Wang

    2005-01-01

    AIM: To study the toxicity of bicyclol to animals.METHODS: Acute toxicity test was performed in Kunming strain mice that were orally given bicyclol at the doses of 3 and 5 g/kg body weight, respectively. Wistar rats were orally administered bicyclol at a dose of 5 g/kg body weight. Death and clinical symptoms of animals were recorded within 7 d. Sub-acute toxicity test was carried out in rats that were treated with various doses of bicyclol (150, 300, 600 mg/kg) once daily for 14 d.Animal behaviors, blood biochemical markers, blood and urine pictures were examined. Chronic toxicity test was conducted in 80 Wistar rats of both sexes. The animals were orally administered with various doses of bicyclol[150, 300, 600 mg/kg, 100-400 folds corresponding to for patients] once daily for 6 mo except for Sunday. The control group was given the same volume of 0.2%sodium carboxyl methylcellulose (Na-CMC). Twenty-one beagle dogs received bicyclol (25, 75, 225 mg/kg, 16.6,50, 150 folds corresponding to the proposed therapeutic dose of bicyclol for patients) once a day for 6 mo except for Sunday. The body weight, food intake, urine and feces, blood picture, blood biochemical markers, and pathological examination of main organs were determined. Mutagenicity and teratogenicity were determined. Mutagenicity assay included Ames's test, chromosome aberration test in CHL cells and micronucleus test in mice. For the teratogenicity assay, pregnant Wistar rats weighing 200-250 g were treated with 0.2, 1.0 g/kg bicyclol once daily from the 7th d of gestation for 10 d.RESULTS: The oral LD50 of bicyclol was over 5 g/kg in mice and rats. No noticeable alterations in subacute and chronic toxicity of rats and dogs were demonstrated. No mutagenicity and teratogenicity of bicyclol were found.CONCLUSION: Bicyclol has no detectable chronic toxicity as well as mutagenicity and teratogenicity in animals.

  15. The use of pig hepatocytes for biotransformation and toxicity studies

    NARCIS (Netherlands)

    Hoogenboom, L.A.P.

    1991-01-01

    The three main objectives of this study were, (1) to investigate the possibility to isolate viable hepatocytes from liver samples of pigs, (2) to study their use for biotransformation and toxicity studies, and (3) to demonstrate the value of this model, in particular in the field of residue

  16. The use of pig hepatocytes for biotransformation and toxicity studies.

    NARCIS (Netherlands)

    Hoogenboom, L.A.P.

    1991-01-01

    The three main objectives of this study were, (1) to investigate the possibility to isolate viable hepatocytes from liver samples of pigs, (2) to study their use for biotransformation and toxicity studies, and (3) to demonstrate the value of this model, in particular in the field of residue toxicolo

  17. The use of whole food animal studies in the safety assessment of genetically modified crops: limitations and recommendations.

    Science.gov (United States)

    Bartholomaeus, Andrew; Parrott, Wayne; Bondy, Genevieve; Walker, Kate

    2013-11-01

    There is disagreement internationally across major regulatory jurisdictions on the relevance and utility of whole food (WF) toxicity studies on GM crops, with no harmonization of data or regulatory requirements. The scientific value, and therefore animal ethics, of WF studies on GM crops is a matter addressable from the wealth of data available on commercialized GM crops and WF studies on irradiated foods. We reviewed available GM crop WF studies and considered the extent to which they add to the information from agronomic and compositional analyses. No WF toxicity study was identified that convincingly demonstrated toxicological concern or that called into question the adequacy, sufficiency, and reliability of safety assessments based on crop molecular characterization, transgene source, agronomic characteristics, and/or compositional analysis of the GM crop and its near-isogenic line. Predictions of safety based on crop genetics and compositional analyses have provided complete concordance with the results of well-conducted animal testing. However, this concordance is primarily due to the improbability of de novo generation of toxic substances in crop plants using genetic engineering practices and due to the weakness of WF toxicity studies in general. Thus, based on the comparative robustness and reliability of compositional and agronomic considerations and on the absence of any scientific basis for a significant potential for de novo generation of toxicologically significant compositional alterations as a sole result of transgene insertion, the conclusion of this review is that WF animal toxicity studies are unnecessary and scientifically unjustifiable.

  18. Sub-chronic toxicity and heavy metal toxicity study on Kappaphycus alvarezii in albino rats

    Institute of Scientific and Technical Information of China (English)

    AbiramiRG; KowsalyaS

    2012-01-01

    Objective: This study aimed to evaluate the toxicity of Kappaphycus alvarezii methanolic extracts in albino rats. Methods: Sub-chronic toxicity was tested with a single dose of intraperitonal administration of the extract as per the OECD guidelines in the experimental group rats and the control group rats was fed with standard diet and water ad libitum. Mortality, behaviour changes, clinical signs and symptoms, food intake, body weight and any abnormalities of the visceral organs were observed. Results: The results revealed that the algal extract resulted in neither mortality nor any abnormalities. The Most of the serum biochemical parameters and hematological values were similar in control and experimental groups, histopathological examination of the vital organs like liver, kidney, spleen, brain and heart revealed no obvious abnormality in the control group and Kappaphycus alvarezii treated group. Conclusion: It may be concluded that Kappaphycus alvarezii rich in nutrient and nutraceutial potentials and also safety food for human consumption.

  19. Four-week oral toxicity study with erythritol in rats

    NARCIS (Netherlands)

    Til, H.P.; Modderman, J.

    1996-01-01

    Erythritol was orally administered to Wistar rats at dietary levels of 0, 5, and 10% for 4 weeks. Soft stools and diarrhea were observed in male and female animals of the 10% group and in female animals of the 5% group. These symptoms disappeared during the course of the study. Mean body weights of

  20. Four-week oral toxicity study with erythritol in rats

    NARCIS (Netherlands)

    Til, H.P.; Modderman, J.

    1996-01-01

    Erythritol was orally administered to Wistar rats at dietary levels of 0, 5, and 10% for 4 weeks. Soft stools and diarrhea were observed in male and female animals of the 10% group and in female animals of the 5% group. These symptoms disappeared during the course of the study. Mean body weights of

  1. Diversity and Biosynthetic Potential of Culturable Microbes Associated with Toxic Marine Animals

    Directory of Open Access Journals (Sweden)

    Brett A. Neilan

    2013-08-01

    Full Text Available Tetrodotoxin (TTX is a neurotoxin that has been reported from taxonomically diverse organisms across 14 different phyla. The biogenic origin of tetrodotoxin is still disputed, however, TTX biosynthesis by host-associated bacteria has been reported. An investigation into the culturable microbial populations from the TTX-associated blue-ringed octopus Hapalochlaena sp. and sea slug Pleurobranchaea maculata revealed a surprisingly high microbial diversity. Although TTX was not detected among the cultured isolates, PCR screening identifiedsome natural product biosynthesis genes putatively involved in its assembly. This study is the first to report on the microbial diversity of culturable communities from H. maculosa and P. maculata and common natural product biosynthesis genes from their microbiota. We also reassess the production of TTX reported from three bacterial strains isolated from the TTX-containing gastropod Nassarius semiplicatus.

  2. Strategic focus on 3R principles reveals major reductions in the use of animals in pharmaceutical toxicity testing.

    Directory of Open Access Journals (Sweden)

    Elin Törnqvist

    Full Text Available The principles of the 3Rs, Replacement, Reduction and Refinement, are being increasingly incorporated into legislations, guidelines and practice of animal experiments in order to safeguard animal welfare. In the present study we have studied the systematic application of 3R principles to toxicological research in the pharmaceutical industry, with particular focus on achieving reductions in animal numbers used in regulatory and investigatory in vivo studies. The work also details major factors influencing these reductions including the conception of ideas, cross-departmental working and acceptance into the work process. Data from 36 reduction projects were collected retrospectively from work between 2006 and 2010. Substantial reduction in animal use was achieved by different strategies, including improved study design, method development and project coordination. Major animal savings were shown in both regulatory and investigative safety studies. If a similar (i.e. 53% reduction had been achieved simultaneously within the twelve largest pharmaceutical companies, the equivalent reduction world-wide would be about 150,000 rats annually. The results point at the importance of a strong 3R culture, with scientific engagement, collaboration and a responsive management being vital components. A strong commitment in leadership for the 3R is recommended to be translated into cross-department and inter-profession involvement in projects for innovation, validation and implementation. Synergies between all the three Rs are observed and conclude that in silico-, in vitro- and in vivo-methods all hold the potential for applying the reduction R and should be consequently coordinated at a strategic level.

  3. Strategic focus on 3R principles reveals major reductions in the use of animals in pharmaceutical toxicity testing.

    Science.gov (United States)

    Törnqvist, Elin; Annas, Anita; Granath, Britta; Jalkesten, Elisabeth; Cotgreave, Ian; Öberg, Mattias

    2014-01-01

    The principles of the 3Rs, Replacement, Reduction and Refinement, are being increasingly incorporated into legislations, guidelines and practice of animal experiments in order to safeguard animal welfare. In the present study we have studied the systematic application of 3R principles to toxicological research in the pharmaceutical industry, with particular focus on achieving reductions in animal numbers used in regulatory and investigatory in vivo studies. The work also details major factors influencing these reductions including the conception of ideas, cross-departmental working and acceptance into the work process. Data from 36 reduction projects were collected retrospectively from work between 2006 and 2010. Substantial reduction in animal use was achieved by different strategies, including improved study design, method development and project coordination. Major animal savings were shown in both regulatory and investigative safety studies. If a similar (i.e. 53%) reduction had been achieved simultaneously within the twelve largest pharmaceutical companies, the equivalent reduction world-wide would be about 150,000 rats annually. The results point at the importance of a strong 3R culture, with scientific engagement, collaboration and a responsive management being vital components. A strong commitment in leadership for the 3R is recommended to be translated into cross-department and inter-profession involvement in projects for innovation, validation and implementation. Synergies between all the three Rs are observed and conclude that in silico-, in vitro- and in vivo-methods all hold the potential for applying the reduction R and should be consequently coordinated at a strategic level.

  4. Six Month Oral Toxicity Study of WR238605 Succinate in Rats. Volume 2

    Science.gov (United States)

    1996-02-02

    STUDY MO: 1!>2 ABBR: HCV SEX: FEMALE UNITS: fL Animal ID Week U Week 13 Week 26 GROUP: 1-F:0 mg base/kg/day 426 57.8 55.4 57.9 427 58.8 55.5 57.5...Microscopic (Micro) Findings (Section V). The codes used as entries in these tables are explained in the Report Codes Table. The results of the bone...TOXICITY STUDY OF WR23 8605 SUCCINATE IN RATS SUMMARY OF CLINICAL CHEMISTRY TESTS TEST: Creatine Kinase [uj Ul STUDY ID: UIC-15B STUDY NO

  5. Per- and polyfluoro toxicity (LC(50) inhalation) study in rat and mouse using QSAR modeling.

    Science.gov (United States)

    Bhhatarai, Barun; Gramatica, Paola

    2010-03-15

    Fully or partially fluorinated compounds, known as per- and polyfluorinated chemicals are widely distributed in the environment and released because of their use in different household and industrial products. Few of these long chain per- and polyfluorinated chemicals are classified as emerging pollutants, and their environmental and toxicological effects are unveiled in the literature. This has diverted the production of long chain compounds, considered as more toxic, to short chains, but concerns regarding the toxicity of both types of per- and polyfluorinated chemicals are alarming. There are few experimental data available on the environmental behavior and toxicity of these compounds, and moreover, toxicity profiles are found to be different for the types of animals and species used. Quantitative structure-activity relationship (QSAR) is applied to a combination of short and long chain per- and polyfluorinated chemicals, for the first time, to model and predict the toxicity on two species of rodents, rat (Rattus) and mouse (Mus), by modeling inhalation (LC(50)) data. Multiple linear regression (MLR) models using the ordinary-least-squares (OLS) method, based on theoretical molecular descriptors selected by genetic algorithm (GA), were used for QSAR studies. Training and prediction sets were prepared a priori, and these sets were used to derive statistically robust and predictive (both internally and externally) models. The structural applicability domain (AD) of the model was verified on a larger set of per- and polyfluorinated chemicals retrieved from different databases and journals. The descriptors involved, the similarities, and the differences observed between models pertaining to the toxicity related to the two species are discussed. Chemometric methods such as principal component analysis (PCA) and multidimensional scaling (MDS) were used to select most toxic compounds from those within the AD of both models, which will be subjected to experimental tests

  6. [Studies of the tolerance and toxicity of Luzern-green-meal pellets after selenium fertilization].

    Science.gov (United States)

    Berschneider, F; Hess, M; Neuffer, K; Willer, S

    1977-12-01

    In a feeding trial, rabbits allotted in 3 experimental groups were fed rations containing 2.09, 9.83 and 19.5 mg selenium/kg feed in the form of selenium-enriched alfalfa green meal pellets. The selenium enrichment was done by foliar application (spraying) of the 20--25 cm high plant stand with 2.5 kg SeO2 per hectare in watery solution. The control animals were given normal alfalfa green meal pellets of 0.16 ppm selenium content. Toxicity and lethality, tolerance limit and nutritive effect of the pellets were studied. Plant-assimilated selenium was found to be converted more efficiently by the animal organism than was selenium from inorganic compounds (higher retention rate, better gain in body weight and lower feed expenditure). Therefore, the selenium supply to farm animals should be improved by feeding crops that were given selenium dressings.

  7. Fourteen-Day Subacute Intravenous Toxicity Study of Hypertonic Saline/ Dextran 70 and its Constituents in Beagle Dogs

    Science.gov (United States)

    1989-11-01

    in various animal models (G. Jonsson, Pharmacia Pharmaceuticals AB, personal communication). Signs were most likely due to the transient derangement...standard laboratory model for subacute toxicity studies and is accepted by all regulatory agencies. Zaucha et al.--137 Appendix C: HISTORICAL LISTING OF...cephalic vein from all treatment and dosage groups had lesions which resulted from repeated intravenous injections; qualitative or cuantitative

  8. Study on the Potential Toxicity of a Thymoquinone-Rich Fraction Nanoemulsion in Sprague Dawley Tats

    Directory of Open Access Journals (Sweden)

    Maznah Ismail

    2013-06-01

    Full Text Available Toxicological studies constitute an essential part of the effort in developing an herbal medicine into a drug product. A newly developed thymoquinone-rich fraction nanoemulsion (TQRFNE has been prepared using a high pressure homogenizer. The purpose of this study was to investigate the potential acute toxicity of this nanoemulsion in Sprague Dawley rats. The acute toxicity studies were conducted as per the OECD guidelines 425, allowing for the use of test dose limit of 20 mL TQRFNE (containing 44.5 mg TQ/kg. TQRFNE and distilled water (DW as a control were administered orally to both sexes of rats on Day 0 and observed for 14 days. All the animals appeared normal, and healthy throughout the study. There was no observed mortality or any signs of toxicity during the experimental period. The effects of the TQRFNE and DW groups on general behavior, body weight, food and water consumption, relative organ weight, hematology, histopathology, and clinical biochemistry were measured. All the parameters measured were unaffected as compared to the control (DW group. The administration of 20 mL TQRFNE /kg was not toxic after an acute exposure.

  9. A Study on Impact of Anime on Tourism in Japan : A Case of "Anime Pilgrimage"

    OpenAIRE

    Okamoto, Takeshi

    2009-01-01

    Recently, in Japan, some of anime fans make "Anime Pilgrimage" which is a kind of tourist behavior. People making an "Anime Pilgrimage" are called "Anime Pilgrims". Some cases of "Anime Pilgrimage" evolve into movement of regional development. In these cases "Anime Pilgrims" collaborate with local residents spontaneously, hold an event and make souvenir or goods. The objective of this paper is to clarify characteristics of "Anime Pilgrim" using questionnaire survey and face-to-face interviews.

  10. Larvicidal activity of the water extract of Moringa oleifera seeds against Aedes aegypti and its toxicity upon laboratory animals

    Directory of Open Access Journals (Sweden)

    Paulo M.P. Ferreira

    2009-06-01

    Full Text Available In this work, biological effects of the water extract of Moringa oleifera seeds (WEMOS were assessed on eggs and 3rd instar larvae of Aedes aegypti and on its toxicity upon laboratory animals (Daphnia magna, mice and rats. Crude WEMOS showed a LC50 value of 1260µg/mL, causing 99.2 ± 2.9% larvae mortality within 24 h at 5200µg/mL, though this larvicidal activity has been lost completely at 80ºC/10 min. WEMOS did not demonstrate capacity to prevent egg hatching. After extensive dialyses of the crude WEMOS into watersoluble dialyzable (DF and nondyalizable (NDF fractions, only DF maintained its efficacy to kill larvae. Acute toxicity evaluations on daphnids (EC50 of 188.7µg/mL and mice (LD50 of 446.5 mg/kg body weight pointed out to low toxicity. Despite the thymus hypertrophy, WEMOS revealed to be harmless in orally and subacutelytreated rats. In conclusion, WEMOS has thermostable bioactive compounds against Ae. aegypti larvae with apparent molecular mass lower than 12 kDa and moderately toxic potential.Neste trabalho, o extrato aquoso das sementes de Moringaoleifera (EASMO foi avaliado quanto aos seus efeitos biológicos sobre ovos e larvas de Aedes aegypti no 3ºestágio de desenvolvimento e sua toxicidade sobre animais de laboratório(Daphnia magna, camundongos e ratos. O EASMO bruto revelou uma CL50 de 1.260 µg/mL, causando 99, 2 ± 2, 9% de mortalidade em 24 h na concentração de 5.200 µg/mL, embora o mesmo não tenha sido capaz de impedir a eclosão dos ovos. A atividade larvicida extinguiu-se após aquecimento do extrato a 80ºC/10 min. Diálises sucessivas do EASMO bruto resultaram em duas frações solúveis em água (Fração dializável, FD; Fração nãodializável, FND, dentre as quais apenas a FD mostrou ação larvicida. Testes de toxicidade aguda realizadosem dáfnias (CE50 de 188, 7 µg/mL e camundongos (DL50 de446,5 mg/kg de peso corpóreo evidenciaram baixa toxicidade. Apesar da hipertrofia tímica, o EASMO mostrou ser

  11. Animal subjectivity: a study into philosophy and theory of animal experience.

    NARCIS (Netherlands)

    Lijmbach, S.E.E.M.

    1998-01-01

    For many people, laypeople as well as animal scientists and philosophers, animal welfare involves animal feelings. Scientifically, however, animal feelings are problematic. In the concluding remarks of a conference about the welfare of domestic animals in 1994, for example, two questions for further

  12. Animal subjectivity : a study into philosophy and theory of animal experience

    NARCIS (Netherlands)

    Lijmbach, S.

    1998-01-01

    For many people, laypeople as well as animal scientists and philosophers, animal welfare involves animal feelings. Scientifically, however, animal feelings are problematic. In the concluding remarks of a conference about the welfare of domestic animals in 1994, for example, two questions fo

  13. Animal subjectivity : a study into philosophy and theory of animal experience

    NARCIS (Netherlands)

    Lijmbach, S.

    1998-01-01

    For many people, laypeople as well as animal scientists and philosophers, animal welfare involves animal feelings. Scientifically, however, animal feelings are problematic. In the concluding remarks of a conference about the welfare of domestic animals in 1994, for example, two questions

  14. PHYTOCHEMICAL AND TOXICITY STUDY OF EMBLICA OFFICINALIS (AMLA

    Directory of Open Access Journals (Sweden)

    Pandey Govind

    2011-03-01

    Full Text Available In the present study, phytochemistry and toxicities (acute and chronic of Emblica officinalis fruit (Amla have been determined. The hydroalcoholic extract (HAE of amla was prepared and its extractability was found to be 46.9%. Different chemical tests showed the presence of various active principles or phytoconstituents, viz., alkaloids, glycosides, reducing sugars, tannins, resins, saponins, sterols and fixed oils. For acute toxicity, including median lethal dose (LD50 of amla, its HAE was administered @ 250, 500 and 1000 mg/kg body weight to female albino rats of groups 2 to 4, respectively. Rats of group 1 were given normal saline to serve as control. There was no mortality up to 48 hr, hence this drug showed the LD50 above 1000 mg/kg. For chronic toxicity of E. officinalis HAE, similar drug dosage schedule was applied in groups 1 to 4 of rats as used for acute toxicity study; however, the drug was given for 3 weeks. During this period, E. officinalis did not cause any untoward effect.

  15. GAPs in the study of zoo and wild animal welfare.

    Science.gov (United States)

    Goulart, Vinícius D; Azevedo, Pedro G; van de Schepop, Joanna A; Teixeira, Camila P; Barçante, Luciana; Azevedo, Cristiano S; Young, Robert J

    2009-11-01

    To investigate the science of animal welfare for zoo and wild animals in the period from 1966 to 2007, we conducted a bibliometric analysis of abstracts downloaded from The Web of Science((c)) database using the keyword combination "Animal welfare, Zoo* and wild" in the topic field. In total we downloaded 1,125 abstracts, which were classified into the following categories: year of publication; environment of the study (e.g., zoo) or theoretical; area of knowledge (e.g., conservation in situ); number of experimental animals used; species; addresses of authors; taxonomic classification; publication language; journal name; number of citations received. Since 1990, there has been a rapid increase in the number of articles published in this area of animal welfare. One worrying result was that published articles were predominately of a theoretical nature (58.65%, N=563). Most of the articles were published by authors either in Europe (47.43%, N=480) or North America (37.65%, N=381) and written in English (87.71%, N=971). The majority of experimental studies were conducted with mammals (75.92%, N=391), and had small sample sizes (N=7 for zoo-based studies). In terms of impact factor (IF), the journals in this study had a median factor equivalent to that for the area of biological sciences (median IF=1.013). Little knowledge cross-over from farm animal welfare was found (only four articles) in this study. In conclusion, zoo and wild animal welfare as a science may benefit from a greater interaction with farm animal welfare.

  16. In vivo Toxicity Studies on Gall Extracts of Terminalia chebula (Gaertn.) Retz. (Combretaceae)

    Science.gov (United States)

    Eshwarappa, Ravi Shankara Birur; Ramachandra, Y. L.; Subaramaihha, Sundara Rajan; Subbaiah, Sujan Ganapathy Pasura; Austin, Richard Surendranath; Dhananjaya, Bhadrapura Lakkappa

    2016-01-01

    The galls of Terminala chebula (Gaertn.) Retz. (Combretaceae) are used for the treatment of various diseases in folk medicine and has been found to posses anti-inflammatory, anti-bacterial, anti-helmintic, anti-tyrosinase, and anti-aging activities. Considering the ethano-botanical and diverse pharmacological applications of galls of T. chebula, in this study, we investigate the possible toxic effects of different gall extracts of T. chebula by Brine shrimp (Artemia salina) toxicity assay. The cytotoxicity test of leaf gall extracts (petroleum ether, chloroform, ethanol, and aqueous) of T. chebula was evaluated by Brine shrimp (A. salina) toxicity assay, which is based on the ability to kill laboratory cultured Artemia nauplii (animals eggs) and also total content of polyphenols, flavonoids with other qualitative phytochemical analysis of the extract were determined. It was observed that the petroleum ether extract was virtually nontoxic on the shrimps, and exhibited very low toxicity with LC50 value of 4356.76 μg/ml. Furthermore, the chloroform extract exhibited very low toxicity, giving LC50 value of 1462.2 μg/ml. On the other hand, the ethanol extract was very toxic to brine shrimps with LC50 value of 68.64 μg/ml. The ethanol extract had the highest total phenolic and flavonoid content of 136 ± 1.5 mg of gallic acid equivalent/g d.w and 113 ± 1.6 mg of quercetin equivalent/g d.w, respectively. The higher toxicity effect was positively correlated to the high content of total polyphenols/flavonoids in the extract. This significant lethality of different extracts to brine shrimp is an indicative of the presence of potent cytotoxic components which warrants further investigation. SUMMARY The present study investigates the toxicity effect of different extracts of galls of T. chebulla, which would serve as an index for formulation of drugs for treatment of various diseases. Presumably, these activities could be attributed in part to the polyphenolic features of

  17. Single dose toxicity and biodistribution studies of [{sup 18}F] fluorocholine

    Energy Technology Data Exchange (ETDEWEB)

    Campos, Danielle C.; Santos, Priscilla F., E-mail: dcc@cdtn.br [Universidade Federal de Minas Gereais (INCT-MM/UFMG), Belo Horizonte, MG (Brazil). Faculdade de Medicina. Instituto Nacional de Ciencia e Tecnologia de Medicina Molecular; Silveira, Marina B.; Ferreira, Soraya Z.; Malamut, Carlos; Silva, Juliana B. da, E-mail: radiofarmacoscdtn@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Unidade de Pesquisa e Producao de Radiofarmacos; Souza, Cristina M.; Campos, Liliane C.; Ferreira, Enio; Araujo, Marina R.; Cassali, Geovanni D., E-mail: cassalig@icb.ufmg.br [Universidade Federal de Minas Gerais (LPC/UFMG), Belo Horizonte, MG (Brazil). Lab. de Patologia Comparada

    2013-07-01

    [{sup 18}F]Fluorocholine ({sup 18}FCH) is a valuable tool for non-invasive diagnosis using positron emission tomography (PET). This radiotracer has been proven to be highly effective in detecting recurrences and staging prostate cancer, diagnoses brain, breast, and esophageal tumors and also hepatocellular carcinoma. The higher uptake of fluorocholine by malignant tumors results from increased choline kinase activity due to accelerated cell multiplication and membrane formation. According to the Brazilian Health Surveillance Agency (ANVISA), radiopharmaceuticals have to be registered before commercialization. The aim of this work was to evaluate single dose toxicity and biodistribution of {sup 18}FCH in mice, since preclinical safety studies are required for register. Experimental procedures were approved by the Ethics Committee on Animal Use (CEUA-IPEN/SP). Single dose toxicity and biodistribution studies were conducted in Swiss mice. No signs of toxicity were observed during clinical trial. No changes in the parameters which were examined, such as: body weight, food consumption, clinical pathology parameters or lesions microscopic were noted. Biodistribution results indicated high physiological tracer uptake in kidney, liver and heart 30 min after injection. Lower activities were recorded in other organs/tissues: pancreas, intestine, spleen, bone, bladder, muscle, brain and blood. Initial preclinical investigations showed no toxic effects of {sup 18}FCH at investigated doses and a biodistribution profile very similar to other reports in literature. This information is essential to support future human trials. (author)

  18. A high throughput live transparent animal bioassay to identify non-toxic small molecules or genes that regulate vertebrate fat metabolism for obesity drug development

    Directory of Open Access Journals (Sweden)

    Woollett Laura A

    2008-08-01

    Full Text Available Abstract Background The alarming rise in the obesity epidemic and growing concern for the pathologic consequences of the metabolic syndrome warrant great need for development of obesity-related pharmacotherapeutics. The search for such therapeutics is severely limited by the slow throughput of animal models of obesity. Amenable to placement into a 96 well plate, zebrafish larvae have emerged as one of the highest throughput vertebrate model organisms for performing small molecule screens. A method for visually identifying non-toxic molecular effectors of fat metabolism using a live transparent vertebrate was developed. Given that increased levels of nicotinamide adenine dinucleotide (NAD via deletion of CD38 have been shown to prevent high fat diet induced obesity in mice in a SIRT-1 dependent fashion we explored the possibility of directly applying NAD to zebrafish. Methods Zebrafish larvae were incubated with daily refreshing of nile red containing media starting from a developmental stage of equivalent fat content among siblings (3 days post-fertilization, dpf and continuing with daily refreshing until 7 dpf. Results PPAR activators, beta-adrenergic agonists, SIRT-1 activators, and nicotinic acid treatment all caused predicted changes in fat, cholesterol, and gene expression consistent with a high degree of evolutionary conservation of fat metabolism signal transduction extending from man to zebrafish larvae. All changes in fat content were visually quantifiable in a relative fashion using live zebrafish larvae nile red fluorescence microscopy. Resveratrol treatment caused the greatest and most consistent loss of fat content. The resveratrol tetramer Vaticanol B caused loss of fat equivalent in potency to resveratrol alone. Significantly, the direct administration of NAD decreased fat content in zebrafish. Results from knockdown of a zebrafish G-PCR ortholog previously determined to decrease fat content in C. elegans support that future GPR

  19. THE STUDY OF CHEMICAL COMPOSITION FOR ANIMAL FATS DURING STORAGE

    OpenAIRE

    Flavia Pop; Cornel Laslo

    2009-01-01

    In this article the chemical composition for 3 types of animal fats (pork fat, beef tallow and buffalo tallow), following the variation of saturated and unsaturated fatty acids proportion during freezing storage was studied. Determination of chemical composition of animal fats is important in establishing organoleptic and physico-chemical parameters, the variation of them in time, nature and proportion of fatty acids conferring specific characteristics to them. For pork fat was determined the...

  20. Progress in Studies of Geomagnetic Navigation of Animals

    Institute of Scientific and Technical Information of China (English)

    Tian Lanxiang; Pan Yongxin; Lin Wei; Wang Yinan; Zhang Shuyi

    2005-01-01

    @@ The geomagnetic field may play a key role in orientation and navigation of many long-distance migratory animals. Taking homing and migrating birds as examples, this paper reviews recent progress in studies of geomagnetic "compass" of animals.Moreover, we propose to address two aspects in future geomagnetic orientation research: ( 1 ) what are the true components of the "map"? (2) What are the magneto-receptors and which brain areas acquire and process the geomagnetic field information ?

  1. Pancreatic exocrine studies in intact animals: historic and current methods.

    Science.gov (United States)

    Niebergall-Roth, E; Teyssen, S; Singer, M V

    1997-12-01

    This report presents a review of the historic and current methods for performing pancreatic exocrine studies in intact animals. Special emphasis is given to the various surgical procedures--pancreatic fistulas, duodenal pouches, and duodenal fistulas--and practice of collecting pancreatic secretion in dogs. Procedures in other animal species--rat, cat, pig, rabbit, cattle, sheep, and horse--also are specified. The advantages and disadvantages, as well as the indications and limitations of the distinct methods, are discussed.

  2. Review of reproductive and developmental toxicity studies with isopropanol.

    Science.gov (United States)

    Faber, Willem D; Pavkov, Kenneth L; Gingell, Ralph

    2008-10-01

    Published studies for reproductive and developmental toxicity conducted with isopropanol have been conducted by the inhalation and oral gavage routes of administration. Interpretation of the data from these studies has resulted in discussions regarding NOAELs and additional benchmark dose modeling publications. Unpublished reproductive and developmental toxicity studies administered in the drinking water were also conducted by BIBRA, and the results of those studies are presented here. In addition, all of the reproductive and developmental toxicity studies conducted with isopropanol are summarized and evaluated for concordance of effects and NOAELs. Endpoints of concern for regulatory agencies were decreases in male mating index and reductions in postnatal pup survival. Original study reports were evaluated and data collated to address these two endpoints, and the data summarized. Data are presented suggesting that there were technical problems in the study that implied a decrease in male mating index, and based on the results from the drinking water studies, the weight of evidence suggests that isopropanol does not affect male mating or fertility at dose levels of up to 1000 mg/kg/day. The weight of evidence suggests that isopropanol can cause decreases in postnatal pup survival following oral gavage administration of 1000-1200 mg/kg/day to the dams. The NOAEL for this endpoint with oral gavage administration was 700 mg/kg/day. Indications of maternal toxicity were also an important predictor for decreased postnatal survival. Decreased postnatal pup survival was also noted in the drinking water studies with isopropanol with a LOAEL of 2278 mg/kg/day and a NOAEL of 1947 mg/kg/day.

  3. Amelioration of Acute Mercury Toxicity by a Novel, Non-Toxic Lipid Soluble Chelator N,N'bis-(2-mercaptoethyl)isophthalamide: Effect on Animal Survival, Health, Mercury Excretion and Organ Accumulation.

    Science.gov (United States)

    Clarke, David; Buchanan, Roger; Gupta, Niladri; Haley, Boyd

    2012-01-01

    The toxic effects of mercury are known to be complex with specific enzyme inhibitions and subsequent oxidative stress adding to the damaging effects. There are likely other factors involved, such as the development of impaired metal ion homeostasis and depletion of thiol and selenium based metabolites such as cysteine and selenium. Much of the toxicity of mercury occurs at the intracellular level via binding of Hg(2+) to thiol groups in specific proteins. Therefore, amelioration of mercury toxicity by the use of chelation would likely be enhanced by the use of a chelator that could cross the cell membrane and the blood brain barrier. It would be most favorable if this compound was of low toxicity, had appropriate pharmacokinetics, bound and rendered mercury cation non-toxic and had antioxidant properties. Herein we report on such a chelator, N,N'-bis(2-mercaptoethyl)isophthalamide (NBMI), and, using an animal model, show that it prevented the toxic effects associated with acute exposure induced by injected mercury chloride.

  4. The classification of motor neuron defects in the zebrafish embryo toxicity test (ZFET) as an animal alternative approach to assess developmental neurotoxicity.

    Science.gov (United States)

    Muth-Köhne, Elke; Wichmann, Arne; Delov, Vera; Fenske, Martina

    2012-07-01

    Rodents are widely used to test the developmental neurotoxicity potential of chemical substances. The regulatory test procedures are elaborate and the requirement of numerous animals is ethically disputable. Therefore, non-animal alternatives are highly desirable, but appropriate test systems that meet regulatory demands are not yet available. Hence, we have developed a new developmental neurotoxicity assay based on specific whole-mount immunostainings of primary and secondary motor neurons (using the monoclonal antibodies znp1 and zn8) in zebrafish embryos. By classifying the motor neuron defects, we evaluated the severity of the neurotoxic damage to individual primary and secondary motor neurons caused by chemical exposure and determined the corresponding effect concentration values (EC₅₀). In a proof-of-principle study, we investigated the effects of three model compounds thiocyclam, cartap and disulfiram, which show some neurotoxicity-indicating effects in vertebrates, and the positive controls ethanol and nicotine and the negative controls 3,4-dichloroaniline (3,4-DCA) and triclosan. As a quantitative measure of the neurotoxic potential of the test compounds, we calculated the ratios of the EC₅₀ values for motor neuron defects and the cumulative malformations, as determined in a zebrafish embryo toxicity test (zFET). Based on this index, disulfiram was classified as the most potent and thiocyclam as the least potent developmental neurotoxin. The index also confirmed the control compounds as positive and negative neurotoxicants. Our findings demonstrate that this index can be used to reliably distinguish between neurotoxic and non-neurotoxic chemicals and provide a sound estimate for the neurodevelopmental hazard potential of a chemical. The demonstrated method can be a feasible approach to reduce the number of animals used in developmental neurotoxicity evaluation procedures.

  5. In vivo toxicity studies of europium hydroxide nanorods in mice.

    Science.gov (United States)

    Patra, Chitta Ranjan; Abdel Moneim, Soha S; Wang, Enfeng; Dutta, Shamit; Patra, Sujata; Eshed, Michal; Mukherjee, Priyabrata; Gedanken, Aharon; Shah, Vijay H; Mukhopadhyay, Debabrata

    2009-10-01

    Lanthanide nanoparticles and nanorods have been widely used for diagnostic and therapeutic applications in biomedical nanotechnology due to their fluorescence and pro-angiogenic properties to endothelial cells, respectively. Recently, we have demonstrated that europium (III) hydroxide [Eu(III)(OH)(3)] nanorods, synthesized by the microwave technique and characterized by several physico-chemical techniques, can be used as pro-angiogenic agents which introduce future therapeutic treatment strategies for severe ischemic heart/limb disease, and peripheral ischemic disease. The toxicity of these inorganic nanorods to endothelial cells was supported by several in vitro assays. To determine the in vivo toxicity, these nanorods were administered to mice through intraperitoneal injection (IP) everyday over a period of seven days in a dose dependent (1.25 to 125 mg kg(-1) day(-1)) and time dependent manner (8-60 days). Bio-distribution of europium elements in different organs was analyzed by inductively coupled plasma mass spectrometry (ICPMS). Short-term (S-T) and long-term (L-T) toxicity studies (mice euthanized on days 8 and 60 for S-T and L-T, respectively) show normal blood hematology and serum clinical chemistry with the exception of a slight elevation of liver enzymes. Histological examination of nanorod-treated vital organs (liver, kidney, spleen and lungs) showed no or only mild histological changes that indicate mild toxicity at the higher dose of nanorods.

  6. A quantum chemical based toxicity study of estimated reduction potential and hydrophobicity in series of nitroaromatic compounds.

    Science.gov (United States)

    Gooch, A; Sizochenko, N; Sviatenko, L; Gorb, L; Leszczynski, J

    2017-02-01

    Nitroaromatic compounds and the products of their degradation are toxic to bacteria, cells and animals. Various studies have been carried out to better understand the mechanism of toxicity of aromatic nitrocompounds and their relationship to humans and the environment. Recent data relate cytotoxicity of nitroaromatic compounds to their single- or two-electron enzymatic reduction. However, mechanisms of animal toxicity could be more complex. This work investigates the estimated reduction and oxidation potentials of 34 nitroaromatic compounds using quantum chemical approaches. All geometries were optimized with density functional theory (DFT) using the solvation model based on density (SMD) and polarizable continuum model (PCM) solvent model protocols. Quantitative structure-activity/property (QSAR/QSPR) models were developed using descriptors obtained from quantum chemical optimizations as well as the DRAGON software program. The QSAR/QSPR equations developed consist of two to four descriptors. Correlations have been identified between electron affinity (ELUMO) and hydrophobicity (log P).

  7. Metabolomics and its application to studying metal toxicity.

    Science.gov (United States)

    Booth, Sean C; Workentine, Matthew L; Weljie, Aalim M; Turner, Raymond J

    2011-11-01

    Here we explain the omics approach of metabolomics and how it can be applied to study a physiological response to toxic metal exposure. This review aims to educate the metallomics field to the tool of metabolomics. Metabolomics is becoming an increasingly used tool to compare natural and challenged states of various organisms, from disease states in humans to toxin exposure to environmental systems. This approach is key to understanding and identifying the cellular or biochemical targets of metals and the underlying physiological response. Metabolomics steps are described and overviews of its application to metal toxicity to organisms are given. As this approach is very new there are yet only a small number of total studies and therefore only a brief overview of some metal metabolomics studies is described. A frank critical evaluation of the approach is given to provide newcomers to the method a clear idea of the challenges and the rewards of applying metabolomics to their research.

  8. Subchronic Toxicity Study of Standardized Methanolic Extract of Mitragyna Speciosa Korth in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Mohd Ulul Ilmie Ahmad Nazri

    2015-06-01

    Full Text Available Mitragyna speciosa Korth, or better known as ketum, has long been used by traditional folk around Southeast Asia to prevent fatigue from working under hot tropical weather and as a replacement of opium, which can then cause addiction. To date, no findings have been reported of the toxic effect of ketum subchronically (28 days. Hence, the aim of this study was to investigate the toxicity of subchronic effect of standardised methanolic extract of ketum (SMEMS in Sprague-Dawley rats. Rats were orally administered with 100, 200, and 500 mg/kg of SMEMS for 28 days. Body weights were recorded daily. They were terminated at day 28 to obtain data for haematology, biochemistry, and histopathology of the brain, liver, kidney, lung, heart, sciatic nerve, and spinal cord. The SMEMS affected body weight compared to control group. Biochemistry findings showed that liver and kidney were affected with the abnormal values in AST, creatinine, globulin, glucose, total protein, and urea. However, SMEMS produced toxic effect more to liver, kidney, and lung than other organs as observed histopathologically. The results suggested subchronic exposure of ketum is toxic to the physiology of the animals.

  9. Comparative In vivo, Ex vivo, and In vitro Toxicity Studies of Engineered Nanomaterials

    Science.gov (United States)

    Efforts to reduce the number of animals in engineered nanomaterials (ENM) toxicity testing have resulted in the development of numerous alternative toxicity testing methods, but in vivo and in vitro results are still evolving and variable. This inconsistency could be due to the f...

  10. Nanosilica and Polyacrylate/Nanosilica: A Comparative Study of Acute Toxicity.

    Science.gov (United States)

    Niu, Ying-Mei; Zhu, Xiao-Li; Chang, Bing; Tong, Zhao-Hui; Cao, Wen; Qiao, Pei-Huan; Zhang, Lin-Yuan; Zhao, Jing; Song, Yu-Guo

    2016-01-01

    We compared the acute toxicity of nanosilica and polyacrylate/nanosilica instillation in Wistar rats (n = 60). Exposure to nanosilica and polyacrylate/nanosilica showed a 30% mortality rate. When compared with saline-treated rats, animals in both exposure groups exhibited a significant reduction of PO2 (P polyacrylate/nanosilica and nanosilica is likely to cause multiple organ toxicity.

  11. Acute Oral Toxicity Study of GAL-57 (Bentazon + Dicamba Herbicide in Rats

    Directory of Open Access Journals (Sweden)

    Dragica Brkić

    2009-01-01

    Full Text Available An acute oral toxicity study of the herbicide GAL-57 (Avalon, a mixture of bentazon and dicamba as active ingredients, was conducted to assess its acute oral toxicity to rats, using a new method that has been used in the past several years (2001. Clinical observations were performed for all animals after different time intervals, and gross necropsy was performed at termination of examination. Clinical symptoms (decreased activity, prone position, abnormal limb position, decreased righting reflex, decreased grip and limb tone, decreased body and abdominal tone and dyspnoea from mild to marked degree were noted after administration of 2000 mg/kg. Animals were found dead 30 minutes to one hour after the treatment. GAL-57 did not cause any clinical sings at single 300 mg/kg bw dose. The physical condition and behaviour of animals were normal during the 14-day observation period. The acute oral LD-50 value of the GAL-57 proved to be between 300 and 2000 mg/kg body weight in rats and was ranked into Poison group III according to Serbian criteria, category 4 of the Global Harmonized Classification System and Category III of the EPA classification.

  12. Tea and cancer prevention: studies in animals and humans.

    Science.gov (United States)

    Chung, Fung-Lung; Schwartz, Joel; Herzog, Christopher R; Yang, Yang-Ming

    2003-10-01

    The role of tea in protection against cancer has been supported by ample evidence from studies in cell culture and animal models. However, epidemiological studies have generated inconsistent results, some of which associated tea with reduced risk of cancer, whereas others found that tea lacks protective activity against certain human cancers. These results raise questions about the actual role of tea in human cancer that needs to be addressed. This article is intended to provide a better perspective on this controversy by summarizing the laboratory studies in animals and humans with emphasis on animal tumor bioassays on skin, lung, mammary glands and colon, and the molecular and cellular mechanisms affected by tea. Finally, a recent small pilot intervention study with green tea in smokers is presented.

  13. ACUTE AND SUBACUTE TOXICITY STUDY ON SPERMATOGENIC SIDDHA DRUG ‘ISAPPUKOL CHOORANAM’ (IC

    Directory of Open Access Journals (Sweden)

    S. Thillaivanan*, K. Kanagavalli , P. Sathiyarajeswaran and P. Parthiban

    2013-11-01

    Full Text Available Herbal medicines have been broadly used in developed countries hence they are natural and comparatively safe. They contain plant materials as their pharmacologically active components. Infertility is one of the most extremely tragic all over the world. Despite recent advances in the treatment of male infertility, the problem has not been satisfactorily tackled. The male infertility is mainly due to an inadequate number of spermatozoa in the semen, the failure of the spermatozoa to move with sufficient vigor towards their goal. Aim of the study is to evaluate the acute and sub-acute toxicity of the spermatogenic siddha drug Isappukol Chooranam (IC (siddha drug.For acute studies, different doses of IC were administered orally to rats once daily for one week. Forsub-acute studies, different doses of IC were administered orally to rats once daily for 28 days in various doses at 50,100,200 mg/kg of body weight. Detailed hematological, biochemical, necropsy and Histopathological evaluation of organs was performed for all animals. Histopathological analysis revealed that Spleen, Testes, Pancreas, Lung, Liver, Brain, Heart, Stomach, Intestine, Bone, Ovary, and Kidney tissues of treated groups did not show any signs of toxicity. No impairment in hepatic, renal, haemopoietic functions were observed throughout the study. No mortality was observed up to 200 mg/kg of body weight in acute and sub-acute toxicity studies.

  14. Where are we in the study of animal emotions?

    Science.gov (United States)

    de Vere, Amber J; Kuczaj, Stan A

    2016-09-01

    The study of emotion is rife with debate over issues as fundamental as how to define emotion, and such disputes are particularly common in the nonhuman animal emotion literature. Here, we seek to address some of these issues, especially in terms of how they relate to animal research. Definitional issues are prevalent; clear definitions are often not given of crucial terms, including 'emotion,' and even where provided, such terms may be used inconsistently throughout a single paper. Further disagreement over the structure of emotions, and the nature of conscious experiences involved, leads to consistent differences in authors' criteria for emotions. We concur with those who believe that animals experience emotions and believe that animal emotions should be studied in their own right, not only as they compare to those of humans. We also propose several avenues for future research that we believe will further our understanding of animal emotions. First, the use of multiple measurement methods to assess emotional responses is most likely to provide the information necessary to distinguish between various states and opens the field to more research in harder-to-study species, such as marine mammals. Second, researchers should also endeavor to increase the range of emotions studied, particularly positive ones, in order to move toward a more balanced range of studied states. Finally, we believe that several aspects of personality research would prove beneficial to the study of animal emotions, particularly the distinction between trait and state emotion and the use of the rating method. WIREs Cogn Sci 2016, 7:354-362. doi: 10.1002/wcs.1399 For further resources related to this article, please visit the WIREs website.

  15. Subchronic toxicity study in mice fed Spirulina maxima.

    Science.gov (United States)

    Salazar, M; Martínez, E; Madrigal, E; Ruiz, L E; Chamorro, G A

    1998-10-01

    The purpose of this study was to evaluate the toxicity of Spirulina maxima, a blue-green alga used as food supplement and food coloring, after 13 weeks of treatment. Groups of ten mice of each sex were given S. maxima in the diet at concentrations of 0 (control), 10, 20 or 30% (w/w) for 13 weeks. The alga ingestion had no effect on behavior, food and water intake, growth or survival. Terminal values in hematology and clinical chemistry did not reveal differences between treated and control groups. However, male and female mice showed significant changes in serum cholesterol levels at 20 and 30% algal concentrations, but a toxic effect of S. maxima was excluded. Post-mortem examination revealed no differences in gross or microscopic findings. Our results show that S. maxima up to high feeding levels did not produce adverse effects in mice after subchronic treatment.

  16. Misonidazole with dexamethasone rescue: an escalating dose toxicity study

    Energy Technology Data Exchange (ETDEWEB)

    Tanasichuk, H.; Urtasun, R.C.; Fulton, D.S.; Raleigh, J.

    1984-09-01

    Neurotoxicity induced by misonidazole (MISO) and desmethylmisonidazole (DMM) has become the dose limiting factor in clinical work. In 1981, the authors reported a preliminary study suggestive that Dexamethasone (DEXA) does have a protective effect against peripheral neuropathies (PN) resulting from toxicity of misonidazole. The authors are presently investigating the use of DEXA, with escalating doses of MISO in an attempt to modify its neurotoxicity. To date, 16 patients have been registered to receive total doses of MISO given in 9 equally divided doses over 3 weeks. DEXA is given 3 days prior to the first dose and continues for the duration of therapy. All patients receive palliative radiation. No toxicity was seen at the total dose of 13.5 gm/M/sub 2/. One grade I PN occurred in the first four patients receiving 15.5 gm/M/sub 2/. Six additional patients were entered at this dose level and no further incidence of PN was observed.

  17. Chronic toxicity study of Hyptis suaveolens (L. Poit in rats

    Directory of Open Access Journals (Sweden)

    Bunjong Chaorai

    2005-09-01

    Full Text Available The effect of water extract of Hyptis suaveolens (H. suaveolens was evaluated for 6-month chronic toxicity in Wistar rats. Control group received distilled water orally 10 ml/kg/day. The extract was orally given to five treatment groups at the doses of 5, 50, 250, 500 and 500 mg/kg/day for 6 months. The last group was served as the recovery group. Changes in the body weights, actual and relative organ weights were not significantly demonstrated in all groups throughout the study. The results of hematological, biochemical parameters and histopathological lesions showed that the extract did not produce any significant doserelated changes. Therefore, it may be concluded that the extract of H. suaveolens at the given doses did not produce any significant toxic effect in rats during 6-month period of the treatment.

  18. Photocatalytic degradation of rosuvastatin: Analytical studies and toxicity evaluations

    Energy Technology Data Exchange (ETDEWEB)

    Machado, Tiele Caprioli, E-mail: tiele@enq.ufrgs.br [Chemical Engineering Department, Federal University of Rio Grande do Sul, Rua Engenheiro Luiz Englert s/n, CEP: 90040-040 Porto Alegre, RS (Brazil); Pizzolato, Tânia Mara [Chemical Institute, Federal University of Rio Grande do Sul, Avenida Bento Gonçalves, 9500, CEP: 91501-970 Porto Alegre, RS (Brazil); Arenzon, Alexandre [Ecology Center, Federal University of Rio Grande do Sul, Avenida Bento Gonçalves, 9500, CEP: 91501-970 Porto Alegre, RS (Brazil); Segalin, Jeferson [Biotechnology Center, Federal University of Rio Grande do Sul, Avenida Bento Gonçalves, 9500, CEP: 91501-970 Porto Alegre, RS (Brazil); Lansarin, Marla Azário [Chemical Engineering Department, Federal University of Rio Grande do Sul, Rua Engenheiro Luiz Englert s/n, CEP: 90040-040 Porto Alegre, RS (Brazil)

    2015-01-01

    Photocatalytic degradation of rosuvastatin, which is a drug that has been used to reduce blood cholesterol levels, was studied in this work employing ZnO as catalyst. The experiments were carried out in a temperature-controlled batch reactor that was irradiated with UV light. Preliminary the effects of the photocatalyst loading, the initial pH and the initial rosuvastatin concentration were evaluated. The experimental results showed that rosuvastatin degradation is primarily a photocatalytic process, with pseudo-first order kinetics. The byproducts that were generated during the oxidative process were identified using nano-ultra performance liquid chromatography tandem mass spectrometry (nano-UPLC–MS/MS) and acute toxicity tests using Daphnia magna were done to evaluate the toxicity of the untreated rosuvastatin solution and the reactor effluent. - Highlights: • The photocatalytic degradation of rosuvastatin was studied under UV irradiation. • Commercial catalyst ZnO was used. • Initial rosuvastatin concentration, photocatalyst loading and pH were evaluated. • The byproducts generated during the oxidative process were detected and identified. • Acute toxicity tests using Daphnia magna were carried out.

  19. [Study on Raman Spectra of Some Animal and Plant Oils].

    Science.gov (United States)

    Wang, Xiang; Dai, Chang-jian

    2015-04-01

    The spectral characteristics of different kinds of oil, either from plant seeds or animal fat, were studied with Raman spectroscopy. The experimental data were processed with the adaptive iteratively reweighted penalized least squares method to realize baseline correction, and provide evident information about their microscopic world. The spectra were analyzed and compared with each other in three parts: the Raman spectra comparison among different samples of plant oils, the analysis of the animal fat and the comparison between plant oils and the animal fat. The differences among the oils were observed in the analysis, including Raman shift and Raman intensity differences. This study not only yields the spectral basis for distinguishing or recognizing the different edible oils, but also confirms that Raman spectroscopy is an effective tool for identifying different oils.

  20. Sub-Chronic Toxicity study of Aqueous extract of Clerodendrum Phlomidis Leaves

    Directory of Open Access Journals (Sweden)

    Gupta Reena

    2012-09-01

    Full Text Available Clerodendrum phlomidis Linn. has been traditionally used for treatment of gynecological disturbances and for agricultural uses. It has been used in many Ayurvedic polyherbal formulations as an immunomodulatory agent. Irrespective of its widespread use, no data on subchronic toxicity has been described. The present study was designed to access sub-chronic toxicity of aqueous extract of Clerodendrum phlomidis leaves. Aqueous extract of Clerodendrum phlomidis leaves was given orally at doses of 200, 400 and 800 mg/kg/day for 90 days for the evaluation of sub-chronic toxicity study. General behavior, mortality, animal body weight, food and water consumption were observed throughout the study period. Hematological, biochemical parameters and histopathological analysis were done at the end of study period. No mortality and abnormal behavior was observed in rats exposed to all the three dose levels. Highest dose produced significant decrease in the red blood cell, hemoglobin and increase in white blood cell count. Biochemical parameters like triglycerides, bilirubin, creatinine and total proteins were significantly altered at high dose. Histopathological findings revealed architectural changes in the liver and kidneys with high dose.

  1. Developmental toxicity study of sodium molybdate dihydrate administered in the diet to Sprague Dawley rats.

    Science.gov (United States)

    Jay Murray, F; Tyl, Rochelle W; Sullivan, Frank M; Tiwary, Asheesh K; Carey, Sandra

    2014-11-01

    Molybdenum is an essential nutrient for humans and animals and is a constituent of several important oxidase enzymes. It is normally absorbed from the diet and to a lesser extent from drinking water and the typical human intake is around 2μg/kg bodyweight per day. No developmental toxicity studies to contemporary standards have been published and regulatory decisions have been based primarily on older studies where the nature of the test material, or the actual dose levels consumed is uncertain. In the current study the developmental toxicity of sodium molybdate dihydrate as a representative of a broad class of soluble molybdenum(VI) compounds, was given in the diet to Sprague Dawley rats in accordance with OECD Test Guideline 414. Dose levels of 0, 3, 10, 20 and 40mgMo/kgbw/day were administered from GD6 to GD20. No adverse effects were observed at any dose level on the dams, or on embryofetal survival, fetal bodyweight, or development, with no increase in malformations or variations. Significant increases in serum and tissue copper levels were observed but no toxicity related to these was observed. The NOAEL observed in this study was 40mgMo/kgbw/day, the highest dose tested.

  2. Genotoxicity test and subchronic toxicity study with Superba™ krill oil in rats

    Directory of Open Access Journals (Sweden)

    Bruce Robertson

    2014-01-01

    Full Text Available The safety of krill oil was assessed in a subchronic toxicity study and in a genotoxicity test. In a 13-week study, rats were fed krill oil or control diets. There were no differences noted in body weight, food consumption or in the functional observation battery parameters in either gender. Differences in both haematology and clinical chemistry values were noted in the krill oil-treated groups. However these findings were of no toxicological significance. Significant decreases in absolute and covariant heart weight in some krill oil-treated animals were noted although no corresponding histological changes were observed. In addition, periportal microvesicular hepatocyte vacuolation was noted histologically in males fed 5% krill oil. This finding was not associated with other indications of hepatic dysfunction. Given that the effects of the 13-week toxicity study were non-toxic in nature, the no observed adverse effect level (NOAEL for the conditions of this study was considered to be 5% krill oil. The genotoxicity experiments documented no mutagenicity of krill oil in bacteria.

  3. EVALUATION OF ACUTE TOXICITY STUDY AND ANTI-ASTHMATIC ACTIVITY OF ZEAL HERBAL GRANULES

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    Bhatt Swati

    2013-06-01

    Full Text Available Objective: To evaluate the Acute toxicity study and Anti-asthmatic activity of Zeal Herbal Granules. Materials & Methods: In the present study, acute toxicity study was carried out as per OECD guideline 423. Anti-asthmatic activity of Zeal Herbal Granules was investigated against compound 48/80-induced mast cell degranulation. Percentage mast cell degranulation was calculated at different concentration level i.e.1, 10, 100 and 1000μg/mL. Results: Zeal Herbal Granules showed significant protection of rat mesenteric mast cells from disruption caused by compound 48/80. Significant dose dependent effect was observed in percentage mast cell degranulation at different dose level of Zeal Herbal Granules in comparison to negative control. 26.83% mast cell degranulation was observed at 100μg/mL dose level of Zeal Herbal Granules. Conclusion: The present study revealed that Zeal Herbal Granules has significant anti-asthmatic activity against compound 48/80-induced mast cell degranulation comparable to that produced by Ketotifen fumarate. There was no lethal and toxic reactions found among the tested animals. Zeal Herbal Granules can be a safe and effective drug for patient with asthmatic complaints.

  4. Lipid emulsions in the treatment of acute poisoning: a systematic review of human and animal studies.

    Science.gov (United States)

    Jamaty, Chloé; Bailey, Benoit; Larocque, Alexandre; Notebaert, Eric; Sanogo, Karine; Chauny, Jean-Marc

    2010-01-01

    To assess the evidence regarding the efficacy and safety of intravenous fat emulsion (IFE) in the management of poisoned patients. We performed a systematic review of the literature with no time or language restriction. The electronic databases were searched from their inception until June 1, 2009 (Medline, EMBASE, ISI web of science, Biological abstract, LILACS, ChemIndex, Toxnet, and Proquest). We also examined the references of identified articles and the gray literature. The target interventions eligible for inclusion were administration of any IFE before, during, or after poisoning in human or animals. All types of studies were reviewed. Eligibility for inclusion and study quality scores, based on criteria by Jadad and the STROBE statement, were evaluated by independent investigators. The primary outcome was mortality. Secondary outcomes included neurologic, hemodynamic, and electrocardiographic variables, as well as adverse effects. Of the 938 publications identified by the search strategies, 74 met the inclusion criteria. We identified 23 animal trials, 50 human, and 1 animal case reports. Overall, the quality of evidence was weak and significant heterogeneity prevented data pooling. Available data suggest some benefits of IFE in bupivacaine, verapamil, chlorpromazine, and some tricyclic antidepressants and beta-blockers toxicity. No trial assessed the safety of IFE in the treatment of acute poisoning. The evidence for the efficacy of IFE in reducing mortality and improving hemodynamic, electrocardiographic, and neurological parameters in the poisoned patients is solely based on animal studies and human case reports. The safety of IFE has not been established.

  5. Clinicopathological Studies on Gentamicin Toxicity in White Leghorn Commercial Layers

    Directory of Open Access Journals (Sweden)

    Najam Ul Islam, M. Zargham Khan1, M. Kashif Saleemi*1, Ahrar Khan1, Sheraz Ahmed Bhatti1, Muhammad Yousaf2 and Zahoor-ul-Hassan3

    2011-10-01

    Full Text Available Gentamicin is an effective and economical drug used to control infectious diseases in poultry but is highly toxic and had slow clearance from the body. This study aimed to report three cases of gentamicin toxicity in three White Leghorn (WLH layer flocks in different poultry producing areas of Pakistan. In first case, gentamicin was injected in a 9000 WLH layer flock @ 10 mg/kg body weight (BW for seven times during 9-15 weeks for age. In second case, gentamicin was injected in a flock of 7500 WLH layers @ 25 mg/kg BW for four times during 17-18 weeks of age. In third case, gentamicin was injected in flock of 16000 WLH layers @ 22.22 mg/kg BW three times in 20-21 weeks of age. Flock wise mortality was 8.69, 82.63 and 71.86%, respectively. Birds were dehydrated, emaciated and had prominent keel bone. Clinical signs included dehydration, decreased body weight leading to emaciation, decreased feed intake, increased water intake and watery diarrhea. Necropsy revealed prominent keal bone, shrunken muscles swollen kidneys bulging out from bony sockets. Petechial and echymotic hemorrhages were present on heart and skeletal muscles. Liver was enlarged with hemorrhagic streaks on its surface. Microscopically, hemorrhages and acute tubular necrosis was recorded in kidneys. Liver had hemorrhages, cellular infiltration and vacuolar (fatty degeneration of hepatocytes. From the results, it could be concluded that overdosing and repeated administration of gentamicin was highly toxic to birds.

  6. A reproducible nonlethal animal model for studying cyanide poisoning.

    Science.gov (United States)

    Vick, J; Marino, M T; von Bredow, J D; Kaminskis, A; Brewer, T

    2000-12-01

    Previous studies using bolus intravenous injections of sodium cyanide have been used to model the sudden exposure to high concentrations of cyanide that could occur on the battlefield. This study was designed to develop a model that would simulate the type of exposure to cyanide gas that could happen during actual low-level continuous types of exposure and then compare it with the bolus model. Cardiovascular and respiratory recordings taken from anesthetized dogs have been used previously to characterize the lethal effects of cyanide. The intravenous, bolus injection of 2.5 mg/kg sodium cyanide provides a model in which a greater than lethal concentration is attained. In contrast, our model uses a slow, intravenous infusion of cyanide to titrate each animal to its own inherent end point, which coincides with the amount of cyanide needed to induce death through respiratory arrest. In this model, therapeutic intervention can be used to restore respiration and allow for the complete recovery of the animals. After recovery, the same animal can be given a second infusion of cyanide, followed again by treatment and recovery, providing a reproducible end point. This end point can then be expressed as the total amount of cyanide per body weight (mg/kg) required to kill. In this study, the average dose of sodium cyanide among 12 animals was 1.21 mg/kg, which is approximately half the cyanide used in the bolus model. Thus, titration to respiratory arrest followed by resuscitation provides a repetitive-use animal model that can be used to test the efficacy of various forms of pretreatment and/or therapy without the loss of a single animal.

  7. PUNARNAVA MANDUR: TOXICITY STUDY OF CLASSICAL AYURVEDIC FORMULATION IN WISTAR RATS

    Directory of Open Access Journals (Sweden)

    P. S. Jamadagni

    2013-06-01

    Full Text Available Punarnava Mandur is an iron containing classical Ayurvedic formulation which was studied for repeated dose oral toxicity study in Wistar rats for 90 days. Total 48 Wistar rats (24 male and 24 female were selected based on the body weight and were randomly distributed into four groups followed by administration of Punarnava Mandur at the dose of 0, 90, 450, 900 mg/kg body weight for 90 consecutive days. Body weight, Weekly Feed and Water consumption, Clinical Chemistry, Hematology, Differential leukocyte Count, Reticulocyte count and Organ weights were recorded and analyzed statistically. At termination, rats were sacrificed, examined for gross pathological changes, organs were collected, weighed and processed for histopathological evaluation. There was no effect on body weights and feed consumption, no abnormal findings in the histopathological evaluation of high dose group animals but there was significant increase in weight of liver in females of high dose group as compared to control. Hence, the dose level 450 mg/kg of Punarnava Mandur was found as NOAEL (No Observable Adverse Effect Level. However, the NOEL (No Observed Effect Level could not be established. It was suggested to carry out a toxicity study at possible higher doses so as to establish target organ of toxicity.

  8. Pain assessment in animal models: do we need further studies?

    Science.gov (United States)

    Gigliuto, Carmelo; De Gregori, Manuela; Malafoglia, Valentina; Raffaeli, William; Compagnone, Christian; Visai, Livia; Petrini, Paola; Avanzini, Maria Antonietta; Muscoli, Carolina; Viganò, Jacopo; Calabrese, Francesco; Dominioni, Tommaso; Allegri, Massimo; Cobianchi, Lorenzo

    2014-01-01

    In the last two decades, animal models have become important tools in understanding and treating pain, and in predicting analgesic efficacy. Although rodent models retain a dominant role in the study of pain mechanisms, large animal models may predict human biology and pharmacology in certain pain conditions more accurately. Taking into consideration the anatomical and physiological characteristics common to man and pigs (median body size, digestive apparatus, number, size, distribution and communication of vessels in dermal skin, epidermal–dermal junctions, the immunoreactivity of peptide nerve fibers, distribution of nociceptive and non-nociceptive fiber classes, and changes in axonal excitability), swines seem to provide the most suitable animal model for pain assessment. Locomotor function, clinical signs, and measurements (respiratory rate, heart rate, blood pressure, temperature, electromyography), behavior (bright/quiet, alert, responsive, depressed, unresponsive), plasma concentration of substance P and cortisol, vocalization, lameness, and axon reflex vasodilatation by laser Doppler imaging have been used to assess pain, but none of these evaluations have proved entirely satisfactory. It is necessary to identify new methods for evaluating pain in large animals (particularly pigs), because of their similarities to humans. This could lead to improved assessment of pain and improved analgesic treatment for both humans and laboratory animals. PMID:24855386

  9. Acute toxicity study of tilmicosin-loaded hydrogenated castor oil-solid lipid nanoparticles

    Directory of Open Access Journals (Sweden)

    Xie Shuyu

    2011-11-01

    Full Text Available Abstract Background Our previous studies demonstrated that tilmicosin-loaded hydrogenated castor oil solid lipid nanoparticles (Til-HCO-SLN are a promising formulation for enhanced pharmacological activity and therapeutic efficacy in veterinary use. The purpose of this work was to evaluate the acute toxicity of Til-HCO-SLN. Methods Two nanoparticle doses were used for the study in ICR mice. The low dose (766 mg/kg.bw with tilmicosin 7.5 times of the clinic dosage and below the median lethal dose (LD50 was subcutaneously administered twice on the first and 7th day. The single high dose (5 g/kg.bw was the practical upper limit in an acute toxicity study and was administered subcutaneously on the first day. Blank HCO-SLN, native tilmicosin, and saline solution were included as controls. After medication, animals were monitored over 14 days, and then necropsied. Signs of toxicity were evaluated via mortality, symptoms of treatment effect, gross and microscopic pathology, and hematologic and biochemical parameters. Results After administration of native tilmicosin, all mice died within 2 h in the high dose group, in the low dose group 3 died after the first and 2 died after the second injections. The surviving mice in the tilmicosin low dose group showed hypoactivity, accelerated breath, gloomy spirit and lethargy. In contrast, all mice in Til-HCO-SLN and blank HCO-SLN groups survived at both low and high doses. The high nanoparticle dose induced transient clinical symptoms of treatment effect such as transient reversible action retardation, anorexy and gloomy spirit, increased spleen and liver coefficients and decreased heart coefficients, microscopic pathological changes of liver, spleen and heart, and minor changes in hematologic and biochemical parameters, but no adverse effects were observed in the nanoparticle low dose group. Conclusions The results revealed that the LD50 of Til-HCO-SLN and blank HCO-SLN exceeded 5 g/kg.bw and thus the

  10. Field Research Studying Whales in an Undergraduate Animal Behavior Laboratory

    Science.gov (United States)

    MacLaren, R. David; Schulte, Dianna; Kennedy, Jen

    2012-01-01

    This work describes a new field research laboratory in an undergraduate animal behavior course involving the study of whale behavior, ecology and conservation in partnership with a non-profit research organization--the Blue Ocean Society for Marine Conservation (BOS). The project involves two weeks of training and five weekend trips on whale watch…

  11. An Exploratory Study of Apache Middle School Students' Computer Animation.

    Science.gov (United States)

    Stokrocki, Mary; Buckpitt, Marcia

    The paper describes a participant observation study of a 3 week summer art program for Apache middle school students on the White Mountain Reservation. Computer art skills, specifically animation using a menu-driven computer paint program, were the focus of the investigation. Because it was in the context of a summer program, instruction was…

  12. A European pharmaceutical company initiative challenging the regulatory requirement for acute toxicity studies in pharmaceutical drug development.

    Science.gov (United States)

    Robinson, Sally; Delongeas, Jean-Luc; Donald, Elizabeth; Dreher, David; Festag, Matthias; Kervyn, Sophie; Lampo, Ann; Nahas, Kamil; Nogues, Vicente; Ockert, Deborah; Quinn, Kirsty; Old, Sally; Pickersgill, Nigel; Somers, Kev; Stark, Claudia; Stei, Peter; Waterson, Lynne; Chapman, Kathryn

    2008-04-01

    Regulatory guidelines indicate acute toxicity studies in animals are considered necessary for pharmaceuticals intended for human use. This is the only study type where lethality is mentioned as an endpoint. The studies are carried out, usually in rodents, to support marketing of new drugs and to identify the minimum lethal dose. A European initiative including 18 companies has undertaken an evidence-based review of acute toxicity studies and assessed the value of the data generated. Preclinical and clinical information was shared on 74 compounds. The analysis indicated acute toxicity data was not used to (i) terminate drugs from development (ii) support dose selection for repeat dose studies in animals or (iii) to set doses in the first clinical trials in humans. The conclusion of the working group is that acute toxicity studies are not needed prior to first clinical trials in humans. Instead, information can be obtained from other studies, which are performed at more relevant doses for humans and are already an integral part of drug development. The conclusions have been discussed and agreed with representatives of regulatory bodies from the US, Japan and Europe.

  13. Perinatal Toxicity and Carcinogenicity Studies of Styrene –Acrylonitrile Trimer, A Ground Water Contaminant

    Science.gov (United States)

    Behl, Mamta; Elmore, Susan A.; Malarkey, David E.; Hejtmancik, Milton R.; Gerken, Diane K.; Chhabra, Rajendra S.

    2015-01-01

    Styrene Acrylonitrile (SAN) Trimer is a by-product in the production of acrylonitrile styrene plastics. Following a report of a childhood cancer cluster in the Toms River section of Dover Township, New Jersey, SAN Trimer was identified as one of the groundwater contaminants at Reich Farm Superfund site in the township. The contaminants from the Reich Farm site’s ground water plume impacted two wells at the Parkway well field. The National Toxicology Program (NTP) studied the toxicity and carcinogenicity of SAN Trimer in rats exposed during their perinatal developmental period and adulthood. The chronic toxicity and carcinogenicity studies in F344/N rats were preceded by 7- and 18-week perinatal toxicity studies to determine the exposure concentrations for the 2-year studies. Subsequently, Fisher 344 pregnant dams were exposed to SAN Trimer containing diet at 400, 800, or 1600 ppm concentrations during gestation, nursing and weaning periods of offspring followed by two year of adult exposures to both male and female pups. There was no statistically significant evidence of carcinogenic activity following SAN-Trimer exposure; however, rare neoplasms in the brain and spinal cord were observed in males and to lesser extent in female rats. These incidences were considered within the range of historical background in the animal model used in the current studies. Therefore, the presence of a few rarely occurring CNS tumors in the treated groups were not judged to be associated with the SAN Trimer exposure. The major finding was a dose-related peripheral neuropathy associated with the sciatic nerves in females and spinal nerve roots in males and females thereby suggesting that SAN trimer is potentially a nervous system toxicant. PMID:24060431

  14. Perinatal toxicity and carcinogenicity studies of styrene-acrylonitrile trimer, a ground water contaminant.

    Science.gov (United States)

    Behl, Mamta; Elmore, Susan A; Malarkey, David E; Hejtmancik, Milton R; Gerken, Diane K; Chhabra, Rajendra S

    2013-12-06

    Styrene acrylonitrile (SAN) trimer is a by-product in the production of acrylonitrile styrene plastics. Following a report of a childhood cancer cluster in the Toms River section of Dover Township, New Jersey, SAN Trimer was identified as one of the groundwater contaminants at Reich Farm Superfund site in the township. The contaminants from the Reich Farm site's ground water plume impacted two wells at the Parkway well field. The National Toxicology Program (NTP) studied the toxicity and carcinogenicity of SAN Trimer in rats exposed during their perinatal developmental period and adulthood. The chronic toxicity and carcinogenicity studies in F344/N rats were preceded by 7- and 18-week perinatal toxicity studies to determine the exposure concentrations for the 2-year studies. Subsequently, Fisher 344 pregnant dams were exposed to SAN Trimer containing diet at 400, 800, or 1600ppm concentrations during gestation, nursing and weaning periods of offspring followed by two year of adult exposures to both male and female pups. There was no statistically significant evidence of carcinogenic activity following SAN-Trimer exposure; however, rare neoplasms in the brain and spinal cord were observed in males and to lesser extent in female rats. These incidences were considered within the range of historical background in the animal model used in the current studies. Therefore, the presence of a few rarely occurring CNS tumors in the treated groups were not judged to be associated with the SAN Trimer exposure. The major finding was a dose-related peripheral neuropathy associated with the sciatic nerves in females and spinal nerve roots in males and females thereby suggesting that SAN Trimer is potentially a nervous system toxicant.

  15. [Gymnema sylvestre leaf extract: a 52-week dietary toxicity study in Wistar rats].

    Science.gov (United States)

    Ogawa, Yukio; Sekita, Kiyoshi; Umemura, Takashi; Saito, Minoru; Ono, Atsushi; Kawasaki, Yasushi; Uchida, Osayuki; Matsushima, Yuko; Inoue, Tohru; Kanno, Jun

    2004-02-01

    A 52-week study of oral-repeated-dose toxicity for the extraction powder of Gymnema sylvestre (GS), Indian-native genus, Metaplexis japonica, was conducted in both genders of Wistar rats. The rats were administered a graded dose of GS at 0.01, 0.10 and 1.00% of basal powder diet, along with a group fed solely with the basal powder diet without GS, for 52 weeks. General conditions were recorded daily. Body weights and food consumptions were recorded weekly up to 12 weeks, and thereafter at longer intervals. At 26 weeks, for an intermediate examination, and 52 weeks, for the final examination, animals were subjected to hematology, serum chemistry, and pathological examination. None of the animals died in the period up to 52 weeks. No exposure-related changes in body-weight, in the food consumption, in the hematological examinations, or in the serum biochemical examinations were recognized. No histopathological alterations were seen. Thus, it was concluded that there was no toxic effect in rats treated with GS at up to 1.00% in the diet for 52 weeks. The no-observable-effect level from this study is 1.00% GS, i.e., 504 mg/kg/day for male and 563 mg/kg/day for female as mean daily intake, for 52 weeks.

  16. Antihyperglycemic and subchronic toxicity study of Moringa stenopetala leaves in mice

    Institute of Scientific and Technical Information of China (English)

    Tesemma Sileshi; Eyasu Makonnen; Asfaw Debella; Birhanu Tesfaye

    2014-01-01

    Objective: To evaluate the antihyperglycemic activity and subchronic toxicity of an extract ofMoringa stenopetala(M. stenopetala) leaves in mice. Methods: Antihyperglycemic activities of various solvent subfractions and chromatographic fractions were investigated in alloxan induced diabetic mice. All fractions were administered intragastrically using oral gavage at a dose of 500 mg/kg. For the subchronic toxicity investigation of the 70% ethanol extract of M. stenopetala leaves, a daily dose of 300 or 600 mg/kg body weight was administered to mice over 96 d. Some hematological and plasma biochemical parameters were measured as indices of organ specific toxicity. Preliminary phytochemical screening and antioxidant activity investigation was done using thin layer chromatography method. Results:Among the solvent subfractions of the 70% ethanol extract tested only butanol subfraction exhibited significant reduction of blood glucose level (P Conclusions:The present study revealed that the crude ethanol extract and solvent-solvent fractions as well as chromatographic fractions have antihyperglycemic effect. Furthermore, the crude ethanol extract have some effect on liver of the mice on subchronic administration. Therefore, further study should be done to identify the active principal compound responsible for antihyperglycemic effect and to rule out the safety in other animal model.

  17. Phytochemical Screening and Acute Oral Toxicity Study of Java Tea Leaf Extracts

    Science.gov (United States)

    Safinar Ismail, Intan; Azam, Amalina Ahmad; Abas, Faridah; Shaari, Khozirah; Sulaiman, Mohd Roslan

    2015-01-01

    The term Java tea refers to the decoction of Orthosiphon stamineus (OS) Benth (Lamiaceae) leaves, which are widely consumed by the people in Europe and South East Asian countries. The OS leaves are known for their use in traditional medicinal systems as a prophylactic and curative agent for urinary stone, diabetes, and hypertension and also as a diuretic agent. The present study was aimed at evaluating its possible toxicity. Herein, the major phytochemical constituents of microwave dried OS leaf, which is the common drying process for tea sachets in the market, were also identified. The acute oral toxicity test of aqueous, 50% aqueous ethanolic, and ethanolic extracts of OS was performed at a dose of 5000 mg/Kg body weight of Sprague-Dawley rats. During the 14-day study, the animals were observed for any mortality, behavioral, motor-neuronal abnormalities, body weight, and feed-water consumption pattern. The hematological and serum biochemical parameters to assess the kidney and liver functions were carried out, along with the histological analysis of these organs. It was found that all microwave dried OS leaf extracts did not cause any toxic effects or mortality at the administered dose. No abnormality was noticed in all selected parameters in rats of both sexes as compared with their respective control groups. Thus, the possible oral lethal dose for microwave dried Java tea leaves is more than 5000 mg/Kg body weight. PMID:26819955

  18. Alternative testing strategies for predicting developmental toxicity of antifungal compound

    NARCIS (Netherlands)

    Li, H.

    2016-01-01

    Determination of safe human exposure levels of chemicals in toxicological risk assessments largely relies on animal toxicity data. In these toxicity studies, the highest number of animals are used for reproductive and developmental toxicity testing. Because of economic and ethical reasons, there is

  19. Selective Toxicity of Persian Gulf Sea Cucumber (Holothuria parva and Sponge (Haliclona oculata Methanolic Extracts on Liver Mitochondria Isolated from an Animal Model of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Seydi

    2015-12-01

    Full Text Available Background Natural products isolated from marine environments are well known for their pharmacodynamic potential in diverse disease treatments, such as for cancer or inflammatory conditions. Sea cucumbers are marine animals of the phylum Echinoderm and the class Holothuroidea, with leathery skin and gelatinous bodies. Sponges are important components of Persian Gulf animal communities, and the marine sponges of the genus Haliclona have been known to display broad-spectrum biological activity. Many studies have shown that sea cucumbers and sponges contain antioxidants and anti-cancer compounds. Objectives This study was designed to determine the selective toxicity of Persian Gulf sea cucumber (Holothuria parva and sponge (Haliclona oculata methanolic extracts on liver mitochondria isolated from an animal model of hepatocellular carcinoma, as part of a national project that hopes to identify novel potential anticancer candidates among Iranian Persian Gulf flora and fauna. Materials and Methods To induce hepatocarcinogenesis, rats were given diethylnitrosamine (DEN injections (200 mg/kg i.p. by a single dose, and then the cancer was promoted with 2-acetylaminofluorene (2-AAF (0.02 w/w for two weeks. Histopathological evaluations were performed, and levels of liver injury markers and a specific liver cancer marker (alpha-fetoprotein, were determined for confirmation of hepatocellular carcinoma induction. Finally, mitochondria were isolated from cancerous and non-cancerous hepatocytes. Results Our results showed that H. parva methanolic extracts (250, 500, and 1000 µg/mL and H. oculata methanolic extracts (200, 400, and 800 µg/mL increased reactive oxygen species (ROS formation, mitochondrial membrane potential (MMP, mitochondrial swelling, and cytochrome c release in the mitochondria obtained from cancerous hepatocytes, but not in mitochondria obtained from non-cancerous liver hepatocytes. These extracts also induced caspase-3 activation, which is

  20. Animal performance and economic comparison of novel and toxic endophyte tall fescues to cool-season annuals.

    Science.gov (United States)

    Beck, P A; Gunter, S A; Lusby, K S; West, C P; Watkins, K B; Hubbell, D S

    2008-08-01

    Increased costs of annual establishment of small grain pasture associated with fuel, machinery, and labor are eroding the profitability of stocker cattle enterprises. Interest has therefore increased in development of cool-season perennial grasses that are persistent and high quality. This study occurred on 24 ha (divided into thirty 0.81-ha paddocks) located at the University of Arkansas Division of Agriculture Livestock and Forestry Branch Station, near Batesville. Two tall fescue (Festuca arundinacea Schreb.) cultivars infected with novel endophytes (NE), Jesup infected with AR542 endophyte (Jesup AR542), and HiMag infected with Number 11 endophyte (HM11) were established in September 2002. Jesup AR542 and HM11 were compared with endemic endophyte Kentucky 31 (KY-31) tall fescue; wheat (Triticum aestivum L.) and cereal rye (WR, Secale cereale L.) planted in September 2003, 2004, and 2005; and annual ryegrass [RG, Lolium perenne L. ssp. multiflorum (Lam.) Husnot] planted in September 2004 and 2005. Each year, 3 steers (3.7 steers/ha) were placed on each pasture for fall and winter grazing, and 5 steers (6.2 steers/ha) were placed on each pasture for spring grazing. Animal performance is presented by year in the presence of a year x treatment interaction (P or = 0.14). Body weight gain per hectare was least (P < 0.01) for steers grazing KY-31. Average net return of NE tall fescue was greater (P < 0.01) than KY-31, but profitability of NE did not consistently differ from cool-season annuals. Across the 3-yr study, NE tall fescue produced net returns per hectare of $219; this level of profitability would require 4 yr for a new planting of NE tall fescue to break even. Novel endophyte tall fescues offer potential benefits related to decreased risk of stand establishment of annual forage crops, longer growing season, and acceptable animal performance.

  1. Capping and in vivo toxicity studies of gold nanoparticles

    Science.gov (United States)

    Nghiem, Thi Ha Lien; Tuyen Nguyen, Thi; Fort, Emmanuel; Phuong Nguyen, Thanh; Nhung Hoang, Thi My; Quy Nguyen, Thi; Nhung Tran, Hong

    2012-03-01

    Water-dispersed colloidal gold nanoparticles (AuNPs) with high concentration were synthesized from metal precursor HAuCl4. The bovine serum albumin (BSA) and heterobiofunctionalized thiol polyethylene glycol acid (HS-PEG-COOH) were used as biofunctionalized layers for the synthesized AuNPs. The BSA and HS-PEG-COOH bound to the AuNPs were characterized qualitatively and quantitatively by transmission electron microscope and UV-VS spectrophotometer. The fabricated BSA and HS-PEG-COOH-capped AuNPs were introduced in mouse to study its toxicity and its availability in the liver.

  2. Social Information Transmission in Animals: Lessons from Studies of Diffusion

    Science.gov (United States)

    Duboscq, Julie; Romano, Valéria; MacIntosh, Andrew; Sueur, Cédric

    2016-01-01

    The capacity to use information provided by others to guide behavior is a widespread phenomenon in animal societies. A standard paradigm to test if and/or how animals use and transfer social information is through social diffusion experiments, by which researchers observe how information spreads within a group, sometimes by seeding new behavior in the population. In this article, we review the context, methodology and products of such social diffusion experiments. Our major focus is the transmission of information from an individual (or group thereof) to another, and the factors that can enhance or, more interestingly, inhibit it. We therefore also discuss reasons why social transmission sometimes does not occur despite being expected to. We span a full range of mechanisms and processes, from the nature of social information itself and the cognitive abilities of various species, to the idea of social competency and the constraints imposed by the social networks in which animals are embedded. We ultimately aim at a broad reflection on practical and theoretical issues arising when studying how social information spreads within animal groups. PMID:27540368

  3. Subchronic Inhalation Toxicity Study of n-pentane in Rats.

    Science.gov (United States)

    Kim, Jong-Kyu; Cho, Hae-Won; Han, Jeong-Hee; Lee, Sung-Bae; Chung, Yong-Hyun; Rim, Kyung-Taek; Yang, Jeong-Sun

    2012-09-01

    This study was conducted in order to obtain information concerning the health hazards that may result from a 13 week inhalation exposure of n-pentane in Sprague-Dawley rats. This study was conducted in accordance with the Organization for Economic Co-operation and Development (OECD) guidelines for the testing of chemicals No. 413 'Subchronic inhalation toxicity: 90-day study (as revised in 2009)'. The rats were divided into 4 groups (10 male and 10 female rats in each group), and were exposed to 0, 340, 1,530, and 6,885 ppm n-pentane in each exposure chamber for 6 hour/day, 5 days/week, for 13 weeks. All of the rats were sacrificed at the end of the treatment period. During the test period, clinical signs, mortality, body weights, food consumption, ophthalmoscopy, locomotion activity, urinalysis, hematology, serum biochemistry, gross findings, organ weights, and histopathology were assessed. During the period of testing, there were no treatment related effects on the clinical findings, body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, relative organ weight, and histopathological findings. The no-observable-adverse-effect level (NOAEL) of n-pentane is evaluated as being more than 6,885 ppm (20.3 mg/L) in both male and female rats. n-pentane was not a classified specific target organ toxicity in the globally harmonized classification system (GHS).

  4. STUDIES OF CHOSEN TOXIC ELEMENTS CONCENTRATION IN MULTIFLOWER BEE HONEY

    Directory of Open Access Journals (Sweden)

    Ewa Popiela

    2011-04-01

    Full Text Available 72 544x376 Normal 0 21 false false false  The aim of the study was to determine the bioaccumulation level of chosen toxic elements (Zn, Cu, Pb, As and Cd in multiflower honey collected from Brzeg area. Biological material (honey was mineralized using the microwave technique at an elevated pressure in the microprocessor station of pressure in the type Mars 5. Quantitative analysis of elements (As, Cd, Cu, Pb and Zn was performed by plasma spectrometry method using a Varian ICP-AES apparatus. The presence of toxic elements was determined in examined biological materials. The elements fallowed the fallowing decreasing order with respect to their content of honey: Zn>Cu>Pb>As>Cd. The average concentrations of studied elements observed in multi-flower honey were as follows: 6.24 mg.kg-1 of zinc, 2.75 mg.kg-1 of copper, 0.53, 0.071, 0.042 mg.kg-1of lead, arsenic and cadmium, respectively. Lead was the most problematic in bee honey because its average content exceeded the maximum acceptable concentration. Additionally, this metal concentration was 60% higher in studied samples than allowable standard of lead content.doi:10.5219/134 

  5. Animal Testing

    Science.gov (United States)

    Moretto, Johnny; Chauffert, Bruno; Bouyer, Florence

    The development of a new anticancer drug is a long, complex and multistep process which is supervised by regulatory authorities from the different countries all around the world [1]. Application of a new drug for admission to the market is supported by preclinical and clinical data, both including the determination of pharmacodynamics, toxicity, antitumour activity, therapeutic index, etc. As preclinical studies are associated with high cost, optimization of animal experiments is crucial for the overall development of a new anticancer agent. Moreover, in vivo efficacy studies remain a determinant panel for advancement of agents to human trials and thus, require cautious design and interpretation from experimental and ethical point of views.

  6. E-Cigarettes May Be Less Toxic Than Tobacco, Study Suggests

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_163433.html E-Cigarettes May Be Less Toxic Than Tobacco, Study ... 6, 2017 (HealthDay News) -- Smokers who switch to e-cigarettes can substantially reduce their intake of toxic ...

  7. Reproduction in the space environment: Part I. Animal reproductive studies

    Science.gov (United States)

    Santy, P. A.; Jennings, R. T.; Craigie, D.

    1990-01-01

    Mankind's exploration and colonization of the frontier of space will ultimately depend on men's and women's ability to live, work, and reproduce in the space environment. This paper reviews animal studies, from microorganisms to mammals, done in space or under space-simulated conditions, which identify some of the key areas which might interfere with human reproductive physiology and/or embryonic development. Those space environmental factors which impacted almost all species included: microgravity, artificial gravity, radiation, and closed life support systems. These factors may act independently and in combination to produce their effects. To date, there have been no studies which have looked at the entire process of reproduction in any animal species. This type of investigation will be critical in understanding and preventing the problems which will affect human reproduction. Part II will discuss these problems directly as they relate to human physiology.

  8. Hepatoprotective effect ofSolanum xanthocarpum fruit extract against CCl4 induced acute liver toxicity in experimental animals

    Institute of Scientific and Technical Information of China (English)

    Ramesh K Gupta; Talib Hussain; G Panigrahi; Avik Das; Gireesh Narayan Singh; K Sweety; Md Faiyazuddin; Chandana Venkateswara Rao

    2011-01-01

    Objective:To investigate the hepatoprotective potential ofSolanum xanthocarpum (Solanaceae) (S. xanthocarpum) in experimental rats to validate its traditional claim.Methods: 50%ethanolic fruit extract ofS. xanthocarpum (SXE, 100, 200or400 mg/kg body weight) was administered daily for14days in experimental animals. Liver injury was induced chemically, byCCl4administration (1 mL/kg i.p.).The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase(ALT), Serum alkaline phosphatise (SALP) and total bilirubin. Meanwhile, in vivo antioxidant activities as lipid peroxidation (LPO), reduced glutathione(GSH), superoxide dismutase(SOD) and catalase(CAT) were screened along with histopathological studies.Results: Obtained results demonstrated that the treatment with SXE significantly (P<0.05- <0.001) and dose-dependently prevented chemically induced increase in serum levels of hepatic enzymes. Furthermore,SXE significantly (up toP<0.001) reduced the lipid peroxidation in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and catalase towards normal levels. Histopathology of the liver tissue showed thatSXE attenuated the hepatocellular necrosis and led to reduction of inflammatory cells inflltration. Conclusions: The results of this study strongly indicate the protective effect ofSXE against acute liver injury which may be attributed to its hepatoprotective activity, and there by scientifically support its traditional use.

  9. Animal study for airway inflammation triggered by gastroesophageal reflux

    Institute of Scientific and Technical Information of China (English)

    LAI Yun-gang; WANG Zhong-gao; JI Feng; WU Ji-min; CHEN Xiu; LI Zhen; DONG Shu-kui

    2009-01-01

    Background Gastroesophageal reflux disease with extra-esophageal symptoms, especially those with respiratory istress was attracting more and more attention. The related mechanisms were still in controversy. The purpose of the work was to explore airway inflammation triggered by gastroesophageal reflux.Methods Sixteen Sprague-Dawley rats were used as study group and 9 as control. In the study group, a plastic extender with a trumpet-shaped distal end was inserted into the lower esophagus to dilate the cardia, the pylorus was ligated. One ml of 0.1 mol/L hydrochloric acid was injected into the stomach, While a simple laparotomy was performed for control animals. All animals from two groups were sacrificed 24 hours after operation. Then tracheotomy was carried and the bronchoalveolar lavage fluid was collected in all animals. Cells in the fluid were counted and levels of intedeukin (IL)-5, -6, -8 in it were measured.Results Compared with control group, the study group presented a neutrophil pattem of airway inflammation and an elevated concentration of IL-5, -6, -8 with no significant difference regarding eosinophil count.Conclusion The gastroesophageal reflux-triggered airway inflammation is characterized by a neutrophilic airway inflammation which differed from that caused by asthma, and enhanced levels of IL-5, -6 and -8, which are similar to that caused by asthma.

  10. Role of chronic toxicology studies in revealing new toxicities.

    Science.gov (United States)

    Galijatovic-Idrizbegovic, Alema; Miller, Judith E; Cornell, Wendy D; Butler, James A; Wollenberg, Gordon K; Sistare, Frank D; DeGeorge, Joseph J

    2016-12-01

    Chronic (>3 months) preclinical toxicology studies are conducted to support the safe conduct of clinical trials exceeding 3 months in duration. We have conducted a review of 32 chronic toxicology studies in non-rodents (22 studies in dogs and 10 in non-human primates) and 27 chronic toxicology studies in rats dosed with Merck compounds to determine the frequency at which additional target organ toxicities are observed in chronic toxicology studies as compared to subchronic studies of 3 months in duration. Our review shows that majority of the findings are observed in the subchronic studies since additional target organs were not observed in 24 chronic non rodent studies and in 21 chronic rodent studies. However, 6 studies in non rodents and 6 studies in rodents yielded new findings that were not seen in studies of 3-month or shorter duration. For 3 compounds the new safety findings did contribute to termination of clinical development plans. Although the incidence of compound termination associated with chronic toxicology study observations is low (∼10%), the observations made in these studies can be important for evaluating human safety risk.

  11. STUDY ON MULTIMEDIA ANIMATION SYSTEM OF ACUPOINT ANATOMY WITH FLASH

    Institute of Scientific and Technical Information of China (English)

    WANG Bin; LUO Zhi-yong; PU Yu-feng; HONG Hong; ZUO Zhi-xiong

    2006-01-01

    Mastering anatomic structures of acupoints is of active significance for avoiding blindly needling and preventing accidents of acupuncture and moxibustion. This multimedia animation system of acupoint anatomy adopts Flash software as developing tool and can dynamically display anatomic layers of needle insertion, with objectivity, convenient operation and English-Chinese control, higher reliability, easy to study and master anatomic knowledge of acupoint anatomy, increase teaching efficiency, and richen teaching ways. This system can be used as a teaching tool of acupuncture and moxibustion, a software of studying anatomy of acupoints and an adjuvant tool of medical workers in studying anatomy.

  12. Intracochlear Bleeding Enhances Cochlear Fibrosis and Ossification: An Animal Study.

    Directory of Open Access Journals (Sweden)

    Kyeung A Ryu

    Full Text Available The aim of this study was to investigate the effects of intracochlear bleeding during cochleostomy on cochlear inflammatory response and residual hearing in a guinea pig animal model. Auditory brainstem response threshold shifts were greater in blood injected ears (p<0.05. Interleukin-1β, interleukin-10, tumor necrosis factor-α and nitric oxide synthase 2, cytokines that are related to early stage inflammation, were significantly increased in blood injected ears compared to normal and cochleostomy only ears at 1 day after surgery; with the increased IL-1β being sustained until 3 days after the surgery (p<0.05. Hair cells were more severely damaged in blood injected ears than in cochleostomy only ears. Histopathologic examination revealed more extensive fibrosis and ossification in blood injected ears than cochleostomy only ears. These results show that intracochlear bleeding enhanced cochlear inflammation resulting in increased fibrosis and ossification in an experimental animal model.

  13. Predicting chronic copper and nickel reproductive toxicity to Daphnia pulex-pulicaria from whole-animal metabolic profiles.

    Science.gov (United States)

    Taylor, Nadine S; Kirwan, Jennifer A; Johnson, Craig; Yan, Norman D; Viant, Mark R; Gunn, John M; McGeer, James C

    2016-05-01

    The emergence of omics approaches in environmental research has enhanced our understanding of the mechanisms underlying toxicity; however, extrapolation from molecular effects to whole-organism and population level outcomes remains a considerable challenge. Using environmentally relevant, sublethal, concentrations of two metals (Cu and Ni), both singly and in binary mixtures, we integrated data from traditional chronic, partial life-cycle toxicity testing and metabolomics to generate a statistical model that was predictive of reproductive impairment in a Daphnia pulex-pulicaria hybrid that was isolated from an historically metal-stressed lake. Furthermore, we determined that the metabolic profiles of organisms exposed in a separate acute assay were also predictive of impaired reproduction following metal exposure. Thus we were able to directly associate molecular profiles to a key population response - reproduction, a key step towards improving environmental risk assessment and management.

  14. Muscle pain: animal and human experimental and clinical studies.

    Science.gov (United States)

    Marchettini, P

    1993-10-01

    The search for the identification of the sensory apparatus encoding muscle pain sensation in humans is recounted. Basic neurophysiologic animal studies, leading to a description of slowly conducting afferent from muscle and definition of high threshold polymodal muscle nociceptors, and pioneer psychophysic human studies together with recent microneurographic experiments in humans are described. The phenomena of muscle pain broad localization and distant referral are discussed, and clinical implications are extrapolated to interpret muscle pain as a localizing sign of mononeuropathy or radiculopathy. The identification of human muscle nociceptors has defined the scientific standard to test emerging clinical descriptions having muscle pain as a symptom.

  15. Treatment of textile effluent in a developed phytoreactor with immobilized bacterial augmentation and subsequent toxicity studies on Etheostoma olmstedi fish

    Energy Technology Data Exchange (ETDEWEB)

    Watharkar, Anuprita D. [Department of Biotechnology, Shivaji University, Kolhapur (India); Khandare, Rahul V. [School of Life Sciences, North Maharashtra University, Jalgaon (India); Waghmare, Pankajkumar R.; Jagadale, Ashwini D.; Govindwar, Sanjay P. [Department of Biochemistry, Shivaji University, Kolhapur (India); Jadhav, Jyoti P., E-mail: jpj_biochem@unishivaji.ac.in [Department of Biotechnology, Shivaji University, Kolhapur (India); Department of Biochemistry, Shivaji University, Kolhapur (India)

    2015-02-11

    Graphical abstract: - Highlights: • A phytoreactor was developed and augmented with immobilized bacteria. • This consortium showed enhanced treatment than the individual species. • Oxido-reductases from P. crinitum and B. pumilus could decolorize the effluent. • Characterization of effluent samples endorsed the efficacy of consortial strategy. • Toxicity studies revealed the less toxic nature of the consortium treated effluent. - Abstract: A static hydroponic bioreactor using nursery grown plants of Pogonatherum crinitum along with immobilized Bacillus pumilus cells was developed for the treatment of textile wastewater. Independent reactors with plants and immobilized cells were also kept for performance and efficacy evaluation. The effluent samples characterized before and after their treatment showed that the plant–bacterial consortium reactor was more efficient than those of individual plant and bacterium reactors. COD, BOD, ADMI, conductivity, turbidity, TDS and TSS of the textile effluent was found to be reduced by 78, 70, 93, 4, 90, 13 and 70% respectively within 12 d by the consortial set. HPTLC analysis revealed the transformation of the textile effluent to new products. The phytotoxicity study on Phaeseolus mungo and Sorghum vulgare seeds showed reduced toxicity of treated effluents. The animal toxicity study performed on Etheostoma olmstedi fishes showed the toxic nature of untreated effluent giving extreme stress to fishes leading to death. Histology of fish gills exposed to treated effluent was found to be less affected. The oxidative stress related enzymes like superoxide dismutase and catalase were found to show decreased activities and less lipid peroxidation in fishes exposed to treated effluent.

  16. Safety assessment of Superba™ krill powder: Subchronic toxicity study in rats

    Directory of Open Access Journals (Sweden)

    Kjetil Berge

    2015-01-01

    Full Text Available The safety of krill powder was assessed in a subchronic 13-week toxicity study where rats were fed krill powder or control diets. The krill powder inclusion in the test diet was 9.67% (w/w. There were no differences noted in body weight or food consumption in either gender. Differences in clinical chemistry values were noted in the krill powder-treated animals, but these findings were of no toxicological significance. A significant decrease in absolute heart weight, but not relative heart weight, was observed in both sexes given krill powder, although no corresponding histological changes were observed. Hepatocyte vacuolation was noted histologically in males fed krill powder. This finding was not associated with other indications of hepatic dysfunction. The no observed adverse effect level (NOAEL for the conditions of this study was considered to be 9.67% krill powder.

  17. Recent studies on biomethylation and demethylation of toxic elements.

    Science.gov (United States)

    Ridley, W P; Dizikes, L; Cheh, A; Wood, J M

    1977-08-01

    Methylcobalamin (methyl-B12) has been implicated in the biomethylation of the heavy metals (mercury, tin, platinum, gold, and thallium) as well as the metalloids (arsenic, selenium, tellurium and sulfur). In addition, methylcobalamin has been shown to react with lead, but the lead-alkyl product is unstable in water. Details of the kinetics and mechanisms for biomethylation of arsenic are presented, with special emphasis on synergistic reactions between metal and metalloids in different oxidation states. This study explains why synergistic, or antagonistic, processes can occur when one toxic element reacts in the presence of another. The relative importance of biomethylation reactions involving methylcobalamin will be compared to those reactions where S-adenosylmethionine is involved.

  18. One-generation reproductive toxicity study of DHA-rich oil in rats.

    Science.gov (United States)

    Blum, René; Kiy, Thomas; Waalkens-Berendsen, Ine; Wong, Andrea W; Roberts, Ashley

    2007-12-01

    Polyunsaturated fatty acids, including docosahexaenoic acid (DHA), are natural constituents of the human diet. DHA-algal oil is produced through the use of the marine protist, Ulkenia sp. The reproductive toxicity of DHA-algal oil was assessed in a one-generation study. Rats were provided diets containing DHA-algal oil at concentrations of 1.5, 3.0, or 7.5%, and the control group received a diet containing 7.5% corn oil. Males and females were treated for 10 weeks prior to mating and during mating. Females continued to receive test diets during gestation and lactation. In parental animals, clinical observations, mortality, fertility, and reproductive performance were unaffected by treatment. Differences in food consumption, body weight, and liver weight in the treated groups were not considered to be due to an adverse effect of DHA-algal oil. Spleen weight increases in treated animals were associated with extramedullary hematopoiesis. Yellow discoloration of abdominal adipose tissue was observed in rats from the high-dose group, and histological examination revealed steatitis in all treated parental groups. Exposure to DHA-algal oil did not influence the physical development of F(1) animals. These results demonstrate that DHA-algal oil at dietary concentrations of up to 7.5% in rats does not affect reproductive capacity or pup development.

  19. Preliminary toxicity studies on bis-[beta-(N,N-dimorpholino) ethyl] selenide (MOSE). A new radioimaging agent.

    Science.gov (United States)

    Kostyniak, P J

    1984-01-01

    The present study describes the acute toxicity of MOSE, a proposed radioimaging agent for brain scintigraphy . Acute intraperitoneal administration of MOSE in mice revealed an LD50 between 1.35 and 6.25 g/kg, with convulsions preceding death. Intravenous administration of MOSE in rats resulted in an LD50 between 400 and 800 mg/kg, with death also preceded by convulsions. The rabbit was more sensitive to the acute effects of MOSE than the rat. The LD50 for MOSE given i.v. in the rabbit was 80 mg/kg. The predominant toxic sign was convulsions, which immediately preceded death at high doses. At intermediate doses convulsions were elicited, followed by a period of lethargy which gave way to hyperactivity on the following day. Normal appearances were restored within a week. Hematology and blood chemistries were similar to controls, except for increased serum LDH in animals receiving MOSE when sampled two weeks after dosing. Repeated administration of MOSE by the intravenous route in rabbits at a dose rate of 1 mg/kg/da, five days per week for two weeks, resulted in no signs of toxicity. Hematology, clinical chemistry, and histology revealed no changes in animals receiving MOSE when compared to control. It was concluded that barring any unusual susceptibility in man, the proposed diagnostic dose to man is unlikely to precipitate any acute toxic effects.

  20. Preliminary study for small animal preclinical hadrontherapy facility

    Science.gov (United States)

    Russo, G.; Pisciotta, P.; Cirrone, G. A. P.; Romano, F.; Cammarata, F.; Marchese, V.; Forte, G. I.; Lamia, D.; Minafra, L.; Bravatá, V.; Acquaviva, R.; Gilardi, M. C.; Cuttone, G.

    2017-02-01

    Aim of this work is the study of the preliminary steps to perform a particle treatment of cancer cells inoculated in small animals and to realize a preclinical hadrontherapy facility. A well-defined dosimetric protocol was developed to explicate the steps needed in order to perform a precise proton irradiation in small animals and achieve a highly conformal dose into the target. A precise homemade positioning and holding system for small animals was designed and developed at INFN-LNS in Catania (Italy), where an accurate Monte Carlo simulation was developed, using Geant4 code to simulate the treatment in order to choose the best animal position and perform accurately all the necessary dosimetric evaluations. The Geant4 application can also be used to realize dosimetric studies and its peculiarity consists in the possibility to introduce the real target composition in the simulation using the DICOM micro-CT image. This application was fully validated comparing the results with the experimental measurements. The latter ones were performed at the CATANA (Centro di AdroTerapia e Applicazioni Nucleari Avanzate) facility at INFN-LNS by irradiating both PMMA and water solid phantom. Dosimetric measurements were performed using previously calibrated EBT3 Gafchromic films as a detector and the results were compared with the Geant4 simulation ones. In particular, two different types of dosimetric studies were performed: the first one involved irradiation of a phantom made up of water solid slabs where a layer of EBT3 was alternated with two different slabs in a sandwich configuration, in order to validate the dosimetric distribution. The second one involved irradiation of a PMMA phantom made up of a half hemisphere and some PMMA slabs in order to simulate a subcutaneous tumour configuration, normally used in preclinical studies. In order to evaluate the accordance between experimental and simulation results, two different statistical tests were made: Kolmogorov test and

  1. Pain assessment in animal models: do we need further studies?

    Directory of Open Access Journals (Sweden)

    Gigliuto C

    2014-05-01

    Full Text Available Carmelo Gigliuto,1 Manuela De Gregori,2 Valentina Malafoglia,3 William Raffaeli,3 Christian Compagnone,4 Livia Visai,5,6 Paola Petrini,7 Maria Antonietta Avanzini,9 Carolina Muscoli,8 Jacopo Viganò,11 Francesco Calabrese,11 Tommaso Dominioni,11 Massimo Allegri,2,10 Lorenzo Cobianchi111Anaesthesia and Intensive Care, University of Pavia, Pavia, 2Pain Therapy Service, Fondazione IRCCS Policlinico San Matteo, Pavia, 3ISAL Foundation, Institute for Research on Pain, Torre Pedrera, Rimini, 4Department of Anaesthesia, Intensive Care and Pain Therapy, Azienda Ospedaliera Universitaria Parma, University of Parma, Parma, 5Department of Molecular Medicine, Center for Tissue Engineering (CIT, INSTM UdR of Pavia, University of Pavia, Pavia, 6Department of Occupational Medicine, Ergonomy and Disability, Laboratory of Nanotechnology, Salvatore Maugeri Foundation, IRCCS, Veruno, 7Dipartimento di Chimica, Materiali e Ingegneria Chimica 'G Natta' and Unità di Ricerca Consorzio INSTM, Politecnico di Milano, Milan, 8Department of Health Science, University Magna Grecia of Catanzaro and Centro del Farmaco, IRCCS San Raffaele Pisana, Roma, 9Laboratory of Transplant Immunology/Cell Factory, Fondazione IRCCS Policlinico "San Matteo", Pavia, 10Department of Clinical, Surgical, Diagnostic and Paediatric Sciences, University of Pavia, Pavia, 11University of Pavia, Department of Surgical, Clinical, Paediatric and Diagnostic Science, General Surgery 1, IRCCS Fondazione Policlinico San Matteo, Pavia, ItalyAbstract: In the last two decades, animal models have become important tools in understanding and treating pain, and in predicting analgesic efficacy. Although rodent models retain a dominant role in the study of pain mechanisms, large animal models may predict human biology and pharmacology in certain pain conditions more accurately. Taking into consideration the anatomical and physiological characteristics common to man and pigs (median body size, digestive apparatus

  2. Preliminary phytochemical, acute oral toxicity and antihepatotoxic study of roots of Paeonia officinalis Linn

    Institute of Scientific and Technical Information of China (English)

    Feroz Ahmad; Nahida Tabassum

    2013-01-01

    Objective: To carry out a preliminary phytochemical, acute oral toxicity and antihepatotoxic study of the roots of Paeonia officinalis (P. officinalis) L. Methods: Preliminary phytochemical investigation was done as per standard procedures. Acute oral toxicity study was conducted as per OECD 425 guidelines. The antihepatotoxic activity of aqueous extract of root of P. officinalis was evaluated against carbon tetrachloride (CCl4) induced hepatic damage in rats. Aqueous extract of P. officinalis at the dose levels of 100 and 200 mg/kg body weight was administered daily for 14 d in experimental animals. Liver injury was induced chemically, by CCl4 administration (1 mL/kg i.p.). The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum alkaline phosphatase (SALP), total bilirubin and total protein (TP) along with histopathological studies. Result: Phytochemical screening revealed that the roots ofP. officinalis contain alkaloids, tannins, saponins, glycosides, carbohydrates, flavonoids, terpenes, steroids and proteins. The aqueous extract did not cause any mortality up to 2000 mg/kg. In rats that had received the root extract at the dose of 100 and 200 mg/kg, the substantially elevated AST, ALT, SALP, total bilirubin levels were significantly lowered, respectively, in a dose dependent manner, along with CCl4 while TP levels were elevated in these groups. Histopathology revealed regeneration of the livers in extract treated groups while Silymarin treated rats were almost normal. Conclusions: The aqueous extract of P. officinalis is safe and possesses antihepatotoxic potential.

  3. Integrated in vitro-in silico models for predicting in vivo developmental toxicity : facilitating non-animal based safety assessment

    NARCIS (Netherlands)

    Louisse, J.

    2012-01-01

    In chemical safety assessment, information on adverse effects after repeated dose and chronic exposure to low levels of hazardous compounds is essential for estimating human risks. At present, this information is almost solely obtained by performing animal experiments. Therefore, suitable methods to

  4. [Toxicity studies of Pharmachem's tylosin tartrate for broilers and turkeys].

    Science.gov (United States)

    Donev, B; Angelov, A K; Vitanov, S

    1978-01-01

    Studied were the acute, subchronic, and chronic toxicity of the Pharmachim tylosin tartrate as well as the tolerance of chicken broilers and turkeys. The mean lethal dose of the antibiotic at subcutaneous application to 28-32 day-old broilers was 620 mg/kg; the oral dose was 1500 mg/kg. In the case of 42-45-day-old broilers these values were 740 and 5400 mg/kg. The LD50 at i/v infusion for 75-77-day-old ones was 48 mg/kg. Beside the age and route of introduction toxicity was found to depend on the initial biologic activity of tylosin tartrate. The subcutaneous injection of tylosin tartrate at the rate of 30 mg/kg for 20 days did not lead to changes in the appetite, behaviour, growth, and structure of viscera. A 42-day treatment at the same rate, however, resulted in slightly manifested and fully reversible dystrophic changes in the liver and kidneys. Higher doses (90 and 150 mg/kg) led to transient depression, stunting of growth, and a rise of the urea level and the activity of blood transaminases as well as to moderate destructive changes in the liver and kidneys. The stimulation of growth and the improvement of feed conversion (without deviations in the clinical and biochemical indices of the blood and the structure and development of the viscera in broilers) were recorded after the application of a water-soluble formula of tylosin tartrate for a period of 98 days offered via the drinking water in amounts equal to or exceeding 2 to 4 times the ED50. Turkeys' tolerance for the preparation was evaluated as very good so far as single i/m injective applications were concerned in doses exceeding 3, 5, and 10 times the average effective rates, no differences in this respect being noted with the comparative use of tylosin tartrate produced by the Elanco firm.

  5. Intravenous Toxicity Study of Water-soluble Ginseng Pharmacopuncture in SD Rats

    Directory of Open Access Journals (Sweden)

    Jun-Sang Yu

    2015-12-01

    Full Text Available Objectives: Radix Ginseng has been used for thousands of years to treat a wide variety of diseases. Radix ginseng has also been used as a traditional medicine for boosting Qi energy and tonifying the spleen and lungs. Traditionally, its effect could be obtained orally. Nowadays, a new method, the injection of herbal medicine, is being used. This study was performed to investigate the single-dose intravenous toxicity of water-soluble ginseng pharmacopuncture (WSGP in Sprague-Dawley (SD rats. Methods: All experiments were carried out at Biotoxtech, an institute authorized to perform non-clinical studies under the regulation of Good Laboratory Practice (GLP. At the age of six weeks, 40 SD rats, 20 male rats and 20 female rats, were allocated into one of 4 groups according to the dosages they would receive. The WSGP was prepared in the Korean Pharmacopuncture Institute under the regulation of Korea-Good Manufacturing Practice (K-GMP. Dosages of WSGP were 0.1, 0.5 and 1.0 mL/animal for the experimental groups, and normal saline was administered to the control group. The rat's general conditions and body weights, the results of their hematological and biochemistry tests, and their necropsy and histopathological findings were investigated to identify the toxicological effect of WSGP injected intravenously. The effect was examined for 14 days after the WSGP injection. This study was performed under the approval of the Institutional Animal Ethics Committee of Biotoxtech. Results: No deaths were found in this single-dose toxicity test on the intravenous injection of WSGP, and no significant changes in the rat's general conditions and body weights, the results on their hematological and biochemistry test, and their necropsy findings were observed during the test. The local area of the injection site showed minial change. The lethal dose was assumed to be over 1.0 mL/animal in both sexes. Conclusion: These results indicate that WSGP is safe at dosages up to

  6. PEGylation of superparamagnetic iron oxide nanoparticle for drug delivery applications with decreased toxicity: an in vivo study

    Energy Technology Data Exchange (ETDEWEB)

    Prabhu, Suma [Manipal University, Department of Radiation Biology & Toxicology, School of Life Sciences (India); Mutalik, Srinivas [Manipal University, Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences (India); Rai, Sharada [Manipal University, Department of Pathology, Kasturba Medical College (India); Udupa, Nayanabhirama [Manipal University, Director - Research (Health Sciences) (India); Rao, Bola Sadashiva Satish, E-mail: satishraomlsc@gmail.com, E-mail: rao.satish@manipal.edu [Manipal University, Department of Radiation Biology & Toxicology, School of Life Sciences (India)

    2015-10-15

    Superparamagnetic iron oxide nanoparticles (SPIONs) are evolving as a mainstay across various applications in the field of Science and Technology. SPIONs have enticed attention on the grounds of their unique physicochemical properties as well as potential applications in magnetic hyperthermia, immunoassays, as a contrast agent in magnetic resonance imaging and targeted drug delivery among others. Toward this goal, we synthesized SPIONs by chemical co-precipitation and PEGylated it. PEGylated SPIONs (PS) were studied for its detailed in vivo toxicity profile, in view of further surface engineering for its clinical applications. The intravenous LD{sub 50(14)} of the PS was ascertained as 508.16 ± 41.52 mg/kg b wt. Histopathology of the vital organs of the animals injected with acute toxic doses showed pathological changes in spleen, lung, liver, and kidney. Accumulation of SPION was found in the aforementioned organs as confirmed by Prussian blue staining. Further, 1/10th dose of LD{sub 50(14)} of PS and the Bare SPION (BS) was used to analyze a detailed toxicity profile, including genotoxicity (micronuclei formation and chromosomal aberration assays), organ-specific toxicity (a detailed serum biochemical analysis), and also determination of oxidative stress. The results of toxicity profile indicated no significant toxicity due to systemic exposure of PS. Atomic absorption spectroscopy (AAS) analysis confirmed the accumulation of SPION majorly in lungs, liver spleen, and kidneys. The present study thus indicated an optimal dose of PS which could be used for surface modification for targeted drug delivery applications with least toxicity.

  7. PEGylation of superparamagnetic iron oxide nanoparticle for drug delivery applications with decreased toxicity: an in vivo study

    Science.gov (United States)

    Prabhu, Suma; Mutalik, Srinivas; Rai, Sharada; Udupa, Nayanabhirama; Rao, Bola Sadashiva Satish

    2015-10-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) are evolving as a mainstay across various applications in the field of Science and Technology. SPIONs have enticed attention on the grounds of their unique physicochemical properties as well as potential applications in magnetic hyperthermia, immunoassays, as a contrast agent in magnetic resonance imaging and targeted drug delivery among others. Toward this goal, we synthesized SPIONs by chemical co-precipitation and PEGylated it. PEGylated SPIONs (PS) were studied for its detailed in vivo toxicity profile, in view of further surface engineering for its clinical applications. The intravenous LD50(14) of the PS was ascertained as 508.16 ± 41.52 mg/kg b wt. Histopathology of the vital organs of the animals injected with acute toxic doses showed pathological changes in spleen, lung, liver, and kidney. Accumulation of SPION was found in the aforementioned organs as confirmed by Prussian blue staining. Further, 1/10th dose of LD50(14) of PS and the Bare SPION (BS) was used to analyze a detailed toxicity profile, including genotoxicity (micronuclei formation and chromosomal aberration assays), organ-specific toxicity (a detailed serum biochemical analysis), and also determination of oxidative stress. The results of toxicity profile indicated no significant toxicity due to systemic exposure of PS. Atomic absorption spectroscopy (AAS) analysis confirmed the accumulation of SPION majorly in lungs, liver spleen, and kidneys. The present study thus indicated an optimal dose of PS which could be used for surface modification for targeted drug delivery applications with least toxicity.

  8. A toxicity study of simultaneous administration of Tamoxifen and Diazepam to female Wistar rats.

    Science.gov (United States)

    D'Mello, D; Mehta, D; Pereira, J; Rao, C V

    1999-11-01

    Tamoxifen (TAM) is used in the treatment of breast cancer and decreases the incidence of breast cancer when given to healthy women for different therapeutic purposes. This expansion of its use calls for further studies of its own potential side effects and those in combination with other prescription drugs. Diazepam (DP) is one such drug normally administered to patients who are under cancer treatment and those who suffer from insomnia. The present study examines the effect of individual and simultaneous administration of TAM and DP at therapeutic dose level of 0.8 mg/Kg/day of TAM and 0.3 mg/Kg/day of DP to normal female Wistar rats for a period of 12 weeks. The drugs were administered orally by mixing it in pellet made by wheat dough. There was no significant change in the terminal body weight and liver weights of animals. The ovary weights in TAM + DP treated animals were significantly decreased. The serum succinate dehydrogenase (SDH) levels were significantly lower in TAM, DP and TAM + DP treated rats and comparatively were lowest in TAM and TAM + DP treated animal groups. Serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT), acid and alkaline phosphatase (ACP & ALP) levels were significantly higher in the three treated groups, but comparatively lower in TAM + DP treated animals when compared to TAM or DP alone treated rats. There was marked increase in liver triglyceride and cholesterol levels in the three treated groups but remarkable decrease in liver glycogen. Total serum cholesterol levels were significantly high in DP and TAM + DP treated rats and total serum triglyceride levels were significantly high only in TAM treated rats. As a whole it can be concluded that DP does not enhance TAM toxicity on simultaneous administration, but on its own when administered individually brings about perturbation in lipid storage and metabolism.

  9. Subacute toxicity study on sup(99m)Tc stannous glucoheptonate injection

    Energy Technology Data Exchange (ETDEWEB)

    Belbeck, L.; Bowen, B.M.; Jeu, J.; Richardson, M. (McMaster Univ., Hamilton, Ontario (Canada))

    1981-07-01

    A subacute toxicity study on sup(99m)Tc stannous glucoheptonate was performed with rats, dogs and rabbits, injected intravenously at ten to 100 times the human dose on a body weight basis. There were no abnormalities in the clinical status of any of the animals. No changes were found in urinalysis, blood chemistry or hematology in the rabbits nor in gross examination, renal histology or bone marrow smears in rats and rabbits. Hepatic histology was also done. A focal area of necrosis in a liver of one rabbit that had been injected with 100 times the human dose was observed using light microscopy. Examination by electron microscopy in another group of rats and rabbits was prompted by the observation of that lesion. This revealed vacuolated and dilated smooth endoplasmic reticulum and degranulated and vesiculated rough endoplasmic reticulum in all the test livers. X-ray microanalysis indicates that the ultrastructural changes are linked to the deposition of tin.

  10. Pharmacokinetic and local toxicity studies of liposome-encapsulated and plain mepivacaine solutions in rats.

    Science.gov (United States)

    Tofoli, Giovana Radomille; Cereda, Cíntia Maria Saia; de Araujo, Daniele Ribeiro; de Paula, Eneida; Brito, Rui Barbosa; Pedrazzoli, José; Meurer, Eduardo; Barros, Fábio Alessandro Proença; Groppo, Francisco Carlos; Volpato, Maria Cristina; Ranali, José

    2010-02-01

    The pharmacokinetics and the local toxicity of commercial and liposome-encapsulated mepivacaine formulations injected intra-orally in rats were studied. Animals were divided in groups (n = 4-6) and treated with 0.1 mL of the formulations: 2% mepivacaine with 1:100,000 epinephrine (MVC(2%EPI)), 3% mepivacaine (MVC(3%)), and 2% liposome-encapsulated mepivacaine (MVC(LUV)). The results showed that the 2% liposome-encapsulated mepivacaine reduced C(max), prolonged AUC(0-infinity) and t(1/2) compared with 3% plain and 2% vasoconstritor-associated mepivacaine, after intraoral injection. In addition, it was also observed that liposomal mepivacaine might protect the tissue against local inflammation evoked by plain or vasoconstrictors-associated mepivacaine, giving supporting evidence for its safety and possible clinical use in dentistry.

  11. Chronic toxicity study of cyclohexanone in rats and mice.

    Science.gov (United States)

    Lijinsky, W; Kovatch, R M

    1986-10-01

    A 2-year chronic toxicity assay of cyclohexanone (CAS: 108-94-1) was conducted in F344 rats and (C57BL/6 X C3H)F1 mice by administering a solution of cyclohexanone in drinking water. Two concentrations were given to rats, 6,500 and 3,300 ppm (wt/vol). Male mice received 13,000 and 6,500 ppm, while female mice were given three concentrations, 25,000, 13,000, and 6,500 ppm. Each treatment group consisted of 50 or 52 male and 50 or 52 female rats or mice, except 47 male mice treated with the highest dose and 41 female mice treated with the highest dose, and there was a group of untreated controls of each species. Survival and weight gain were similar to those of controls at the lowest cyclohexanone dose in both sexes of both species, but weight gain was depressed at all of the higher doses. Survival was good (greater than 80% at 90 wk) in all groups except in female mice at the 2 highest doses; at 25,000 ppm of cyclohexanone, only 50% of mice lived beyond 1 year. Most of the neoplasms in the treated groups did not differ significantly in number from those in the controls. Male rats receiving 3,300 ppm cyclohexanone had a 13% incidence of adrenal cortex adenomas (7 animals) compared with an incidence of 2% in controls; the incidence of this neoplasm did not increase in the male rats receiving 6,500 ppm or in the female rats given either dose. The mice had a statistically significant increase in incidence of lymphomas-leukemias among the females given 6,500 ppm, but not among the groups given higher doses of cyclohexanone. Male mice given 6,500 ppm cyclohexanone showed an increased incidence of hepatocellular adenomas and carcinomas, 50% versus 32.5% in controls, but the incidence of these neoplasms was only 37% in the male mice given 13,000 ppm cyclohexanone. The incidence of lymphomas in male mice and of hepatocellular neoplasms in female mice given cyclohexanone did not differ from that in the controls. The evidence for carcinogenic activity of cyclohexanone is

  12. Study of analgesic activity of ethanol extract of Phlogacanthus thyrsiflorus on experimental animal models

    Directory of Open Access Journals (Sweden)

    Apurba Mukherjee

    2009-06-01

    Full Text Available The aim of the study was to evaluate the central and peripheral analgesic action of Phlogacanthus thyrsiflorus in experimental animal models. The extract was prepared by percolation method and acute oral toxicity testing was performed as per OECD guidelines. Analgesic activity was assessed by tail flick method (for central action and glacial acetic acid-induced writhing test (for peripheral action. Leaves extract (500 mg/kg, p.o. and aspirin (100 mg/kg showed significant peripheral analgesic activity (p<0.05. Leaves extract (500 mg/kg, p.o. and pethidine (50 mg/kg, i.p. also showed significant central analgesic activity (p<0.05. Naloxone (1 mg/kg, s.c. was used to find the mechanism of central analgesic action. Some partial agonistic activity for the opioid receptors seems to be probable mechanism of action.

  13. Study of analgesic activity of ethanol extract of Phlogacanthus thyrsiflorus on experimental animal models

    Directory of Open Access Journals (Sweden)

    Apurba Mukherjee, Meghali Chaliha and Swarnamoni Das

    2009-12-01

    Full Text Available The aim of the study was to evaluate the central and peripheral analgesic action of Phlogacanthus thyrsiflorus in experimental animal models. The extract was prepared by percolation method and acute oral toxicity testing was performed as per OECD guidelines. Analgesic activity was assessed by tail flick method (for central action and glacial acetic acid-induced writhing test (for peripheral action. Leaves extract (500 mg/kg, p.o. and aspirin (100 mg/kg showed significant peripheral analgesic activity (p<0.05. Leaves extract (500 mg/kg, p.o. and pethidine (50 mg/kg, i.p. also showed significant central analgesic activity (p<0.05. Naloxone (1 mg/kg, s.c. was used to find the mechanism of central analgesic action. Some partial agonistic activity for the opioid receptors seems to be probable mechanism of action.

  14. Experimental Basis for the High Oral Toxicity of Dinophysistoxin 1: A Comparative Study of DSP

    Directory of Open Access Journals (Sweden)

    Diego A. Fernández

    2014-01-01

    Full Text Available Okadaic acid (OA and its analogues, dinophysistoxin 1 (DTX1 and dinophysistoxin 2 (DTX2, are lipophilic and heat-stable marine toxins produced by dinoflagellates, which can accumulate in filter-feeding bivalves. These toxins cause diarrheic shellfish poisoning (DSP in humans shortly after the ingestion of contaminated seafood. Studies carried out in mice indicated that DSP poisonous are toxic towards experimental animals with a lethal oral dose 2–10 times higher than the intraperitoneal (i.p. lethal dose. The focus of this work was to study the absorption of OA, DTX1 and DTX2 through the human gut barrier using differentiated Caco-2 cells. Furthermore, we compared cytotoxicity parameters. Our data revealed that cellular viability was not compromised by toxin concentrations up to 1 μM for 72 h. Okadaic acid and DTX2 induced no significant damage; nevertheless, DTX1 was able to disrupt the integrity of Caco-2 monolayers at concentrations above 50 nM. In addition, confocal microscopy imaging confirmed that the tight-junction protein, occludin, was affected by DTX1. Permeability assays revealed that only DTX1 was able to significantly cross the intestinal epithelium at concentrations above 100 nM. These data suggest a higher oral toxicity of DTX1 compared to OA and DTX2.

  15. Experimental basis for the high oral toxicity of dinophysistoxin 1: a comparative study of DSP.

    Science.gov (United States)

    Fernández, Diego A; Louzao, M Carmen; Fraga, María; Vilariño, Natalia; Vieytes, Mercedes R; Botana, Luis M

    2014-01-03

    Okadaic acid (OA) and its analogues, dinophysistoxin 1 (DTX1) and dinophysistoxin 2 (DTX2), are lipophilic and heat-stable marine toxins produced by dinoflagellates, which can accumulate in filter-feeding bivalves. These toxins cause diarrheic shellfish poisoning (DSP) in humans shortly after the ingestion of contaminated seafood. Studies carried out in mice indicated that DSP poisonous are toxic towards experimental animals with a lethal oral dose 2-10 times higher than the intraperitoneal (i.p.) lethal dose. The focus of this work was to study the absorption of OA, DTX1 and DTX2 through the human gut barrier using differentiated Caco-2 cells. Furthermore, we compared cytotoxicity parameters. Our data revealed that cellular viability was not compromised by toxin concentrations up to 1 μM for 72 h. Okadaic acid and DTX2 induced no significant damage; nevertheless, DTX1 was able to disrupt the integrity of Caco-2 monolayers at concentrations above 50 nM. In addition, confocal microscopy imaging confirmed that the tight-junction protein, occludin, was affected by DTX1. Permeability assays revealed that only DTX1 was able to significantly cross the intestinal epithelium at concentrations above 100 nM. These data suggest a higher oral toxicity of DTX1 compared to OA and DTX2.

  16. Acute Toxicity Study of Zerumbone-Loaded Nanostructured Lipid Carrier on BALB/c Mice Model

    Directory of Open Access Journals (Sweden)

    Heshu Sulaiman Rahman

    2014-01-01

    Full Text Available Zerumbone- (ZER- loaded nanostructure lipid carrier (NLC (ZER-NLC prepared for its antileukemia effect in vitro was evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200 mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50 of ZER-NLC is higher than 200 mg/kg, thus, safe by oral administration.

  17. Toxicity evaluation of petroleum blending streams: inhalation subchronic toxicity/neurotoxicity study of a light catalytic cracked naphtha distillate in rats.

    Science.gov (United States)

    Lapin, C; Bui, Q; Breglia, R; Koschier, F; Podhasky, P; Lapadula, E; Roth, R; Schreiner, C; White, R; Clark, C; Mandella, R; Hoffman, G

    2001-01-01

    A 15-week, whole-body inhalation study of the vapors of a distillate (LCCN-D) of light catalytic cracked naphtha (CAS no. 64741-55-5, LCCN) was conducted with Sprague-Dawley rats. Target exposure concentrations were 0, 750, 2500, and 7500 ppm for 6 hours/day, 5 days/week. Over the course of the study, animals received at least 65 exposures. For a portion of the control and 7500-ppm groups, a 4-week postexposure period was included in the study. Subchronic toxicity was evaluated using standard parameters. During life, neurotoxicity was evaluated by motor activity assessment and a functional observational battery. Selected tissues from animals in all exposure groups were examined microscopically. Neuropathologic examination of selected neuronal tissues from animals in the control and high-exposure groups was also conducted. No compound-related effects were seen on survival, clinical chemistry, food consumption, or physical signs. No evidence of neurotoxicity was seen at any exposure level. Slight decreases in hematocrit and hemoglobin concentrations were seen in male rats at the end of exposure to 7500 ppm LCCN-D. However, values were within normal physiological ranges and recovery occurred. Slight decreases in mean body weights and body weight gain were observed in high-exposure females during the first 7 weeks of exposure, but this decrease was not seen during the second half of the study. Male rat nephropathy involving hyaline droplet formation and alpha-2micro-globulin accumulation was seen in mid- and high-exposure males, an effect not relevant to humans. The incidence and severity of goblet cell hypertrophy/hyperplasia and respiratory epithelium hyperplasia in nasoturbinal tissues were greater in high-exposure animals, but recovery occurred. None of the effects observed were considered toxicologically significant. The no-observable-adverse-effect level (NOAEL) for subchronic and neurotoxicity of LCCN-D was > or = 7500 ppm.

  18. A Comparative Study of Two Chinese Versions of Animal Farm

    Institute of Scientific and Technical Information of China (English)

    YANG Mei; CHENG Jing

    2016-01-01

    Animal Farm succeeds in establishing George Orwell’s position as a master in literature with its profound moral and hidden but killing sarcasms. And it has been translated into many languages around the world, arousing heated response. So far, there are seventeen versions in China. However, the academic studies focus on the significance of its literary value and political aspects, paying little attention to the systemic study of its translations. The thesis chooses the versions of Rong Rude and Fu Wei-ci and compares them from lexical, syntactical and discourse aspects. Through the comparative study, the author finds out that the two translators apply different translation strategies. Rong tends to adopt foreignization strategy, while Fu is inclined to ap-ply domestication strategy.

  19. Acupuncture points for treating Parkinson's disease based on animal studies.

    Science.gov (United States)

    Kwon, Sunoh; Seo, Byung-Kwan; Kim, Seungtae

    2016-10-01

    Parkinson's disease (PD) is a well-known neurodegenerative disease caused by dopaminergic cell death in the nigrostriatal pathway. Recent studies have shown that acupuncture can be a potential therapy for the treatment of PD, but it is not clear which acupuncture points (acupoints) play major roles in reliving symptoms of PD. Yanglingquan (GB 34), Zusanli (ST 36), Fengfu (GV 16), Taichong (LR 3), Baihui (GV 20) and Dazhui (GV 14) acupoints have frequently been to investigate the effectiveness and action mechanism of acupuncture for treating PD, but it is not clear why they were selected. This review summarizes the current understanding of the acupoints for PD treatment based on Oriental medicine theories and on the accumulated findings from previous animal studies. The results of this study will be useful to development of a strategy for future research in this field.

  20. Insights into restrictive cardiomyopathy from clinical and animal studies

    Institute of Scientific and Technical Information of China (English)

    Pierre-Yves Jean-Charles; Yue-Jin Li; Chang-Long Nan; Xu-Pei Huang

    2011-01-01

    Catdiomyopathies are diseases that primarily affect the myocardium,leading to serious cardiac dysfimction and heart failure.Out of the three major categories of candiomyopathies(hypertrophic,dilated and restrictive),restrictive cardiomyopathy(RCM)is less common and also the least studied However,the prognosis for RCM is poor as some patients dying in their childhood The molecular mechanisms behind the disease development and progression are not very clear and the treatment of RCM is very difficult and often ineffective.In this article,we reviewed the recent progress in RCM research from the clinical studies and the translational studies done on diseased transgenic animal models.This will help for a better understanding of tare mechanisms underlying the etiology and development of RCM and for the design of better treatments for the disease.

  1. Potential for clonal animals in longevity and ageing studies.

    Science.gov (United States)

    Nilsson Sköld, Helen; Obst, Matthias

    2011-10-01

    Ageing is defined as a decline in reproductive and/or somatic performance over time, and as such is experienced by most organisms. Evolutionary theories explain ageing as a consequence of reduced selection pressure against mutations and reduced allocation to somatic maintenance in post-reproductive individuals. In addition, the fecundity of younger age-groups makes a more significant contribution than infinite maintenance of the parental body to the production of subsequent generations. However, in clonal animals, as well as in plants that reproduce by agametic cloning, the adult body is itself a reproductive unit that increases its fitness as a function of genet size. Given the apparent longevity of many such clonal organisms, species undergoing agametic cloning are often assumed to be non-ageing and even potentially immortal. Here, we present a brief overview of ageing in organisms undergoing agametic cloning, focusing on animals and molecular investigation. We discuss molecular and evolutionary aspects of ageing or non-ageing with respect to selection in clonal species. Of particular relevance to the search for potential mechanistic processes behind longevity is the notion that clonal organisms are frequently smaller than their obligate sexual counterparts. In conclusion, we find that while clonal animals also commonly age, evolutionary arguments together with empirical evidence suggest that they are likely to be long-lived and stress resistant at the genet level. However, theoretical modeling continues to predict the possibility of immortality, if the contribution from sexual reproduction is low. Future in-depth study of long-lived clones should present an excellent opportunity to discover novel mechanisms for renewal and long-term somatic maintenance and health.

  2. Weight-of-the-evidence review of acrylonitrile reproductive and developmental toxicity studies.

    Science.gov (United States)

    Neal, Barbara H; Collins, James J; Strother, Dale E; Lamb, James C

    2009-01-01

    Risk assessment of acrylonitrile (AN) toxicity to humans has focused on potential carcinogenicity and acute toxicity. Epidemiological studies from China reported reproductive and developmental effects in AN workers, including infertility, birth defects, and spontaneous abortions. A weight-of-the-evidence (WoE) evaluation of the AN database assessed study strength, characterized toxicity, and identified no-observed-adverse-effect levels (NOAELs). The epidemiological studies do not demonstrate causality and are not sufficiently robust to be used for risk assessment. Rodent developmental studies showed fetotoxicity and malformations at maternally toxic levels; there was no unique developmental susceptibility. NOAELs for oral and inhalation exposures were 10 mg/kg/day and 12 ppm (6 h/day), respectively. Drinking-water and inhalation reproductive toxicity studies showed no clear effects on reproductive performance or fertility. Maternally toxic concentrations caused decreased pup growth. The drinking-water reproductive NOAEL was 100 ppm (moderate confidence due to study limitations). The inhalation exposure reproductive and neonatal toxicity high confidence NOAEL was 45 ppm (first generation 90 ppm) (6 h/day). The inhalation reproductive toxicity study provides the most robust data for risk assessment. Based on the WoE evaluation, AN is not expected to be a developmental or reproductive toxicant in the absence of significant maternal toxicity.

  3. Development and Evaluation of Lipid Nanoparticles for Drug Delivery: Study of Toxicity In, Vitro and In Vivo.

    Science.gov (United States)

    Winter, Evelyn; Dal Pizzol, Carine; Locatelli, Claudriana; Crezkynski-Pasa, Tânia Beatriz

    2016-02-01

    Lipid nanoparticles have received considerable attention in the field of drug delivery, due their ability to incorporate lipophilic drugs and to allow controlled drug release. Solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and nanoemulsion (NE) are three different lipid nanostructured systems presenting intrinsically physical properties, which have been widely studied in recent years. Despite the extensive applicability of lipid nanoparticles, the toxicity of these systems has not been sufficiently investigated thus far. It is generally believed that lipids are biocompatible. However, it is known that materials structured in nanoscale might have their intrinsic physicochemical properties modified. Thus, the aim of this study was to evaluate the cytotoxicity of these three nanoparticle systems. To this end, in vitro and in vivo toxicity studies were carried out. Our results indicate that nanoparticles containing the solid lipid GMS (SLN and NLC) induced an important cytotoxicity in vitro, but showed minimal toxicity in vivo--evidenced by the body weight analysis. The NE did not induce in vitro toxicity and did not induce body weight alteration. On the contrary, the SLN and NLC possibly induce an inflammatory process in vivo. All nanoparticle systems induced lipid peroxidation in the animals' livers, but only SLN and NLC induced a decrease of antioxidant defences indicating that the main mechanism of toxicity is the induction of oxidative stress in liver. The higher toxicity induced by SLN and NLC indicates that the solid lipid GMS could be the responsible for this effect. Nevertheless, this study provides important insights for toxicological studies of different lipid nanoparticles systems.

  4. Feasibility study of the zebrafish assay as an alternative method to screen for developmental toxicity and embryotoxicity using a training set of 27 compounds.

    Science.gov (United States)

    Selderslaghs, Ingrid W T; Blust, Ronny; Witters, Hilda E

    2012-04-01

    To anticipate to increased testing needs for reproductive toxicity and 3R approaches, we studied zebrafish embryo/larva as an alternative for animal testing for developmental toxicity and embryotoxicity and evaluated a training set of 27 compounds with a standardized protocol. The classification of compounds in the zebrafish embryo/larva assay, based on a prediction model using a TI (teratogenic index) cut-off value of 2, was compared to available animal and human data. When comparing the classification of compounds in the zebrafish embryo/larva assay to available animal classification, a sensitivity of 72% and specificity of 100% were obtained. The predictive values obtained in comparison to a limited set of human data were 50, 60% respectively for teratogens, non-teratogens. Overall, we demonstrated that the zebrafish embryo/larva assay, may be used as screening tool for prioritization of compounds and could contribute to reduction of animal experiments in the field of developmental toxicology.

  5. Acute and chronic toxicity studies on partially purified hypoglycemic preparation from water extract of bark ofFicus bengalensis.

    Science.gov (United States)

    Gupta, S; Shukla, R; Prabhu, K M; Aggrawal, S; Rusia, U; Murthy, P S

    2002-01-01

    Acute and chronic toxicity studies were conducted to assess toxicity of a partially purified preparation from the water extract of the bark ofFicus bengalensis, which was demonstrated in our earlier studies to have significant hypoglycemic and hypocholesteroiemic effect on alloxan induced, mild and severe diabetes in rabbits. LD(50) of this preparation was found to be ∼1 gm/kg in rats when given orally. For chronic toxicity studies 3 doses of aqueous preparation were given to 3 groups of rats. First group received 5 times ED(50) (50 mg/kg), second group 10 times ED(50) (100 mg/kg) and the third group 15 times ED(50) (150 mg/kg) for 3 months. Fourth group which served as control was given water. After three months, blood was collected for studying biochemical and hematological parameters. Blood glucose, serum cholesterol, liver and kidney function tests, haemoglobin, total and differential leukocyte count were determined. Animals were sacrificed and histopathological examination of liver, heart and kidneys was carried out. Results of the study showed that partially purified preparation fromFicus bengalensis is not toxic by all the above mentioned parameters.

  6. AnimalTFDB 2.0: a resource for expression, prediction and functional study of animal transcription factors.

    Science.gov (United States)

    Zhang, Hong-Mei; Liu, Teng; Liu, Chun-Jie; Song, Shuangyang; Zhang, Xiantong; Liu, Wei; Jia, Haibo; Xue, Yu; Guo, An-Yuan

    2015-01-01

    Transcription factors (TFs) are key regulators for gene expression. Here we updated the animal TF database AnimalTFDB to version 2.0 (http://bioinfo.life.hust.edu.cn/AnimalTFDB/). Using the improved prediction pipeline, we identified 72 336 TF genes, 21 053 transcription co-factor genes and 6502 chromatin remodeling factor genes from 65 species covering main animal lineages. Besides the abundant annotations (basic information, gene model, protein functional domain, gene ontology, pathway, protein interaction, ortholog and paralog, etc.) in the previous version, we made several new features and functions in the updated version. These new features are: (i) gene expression from RNA-Seq for nine model species, (ii) gene phenotype information, (iii) multiple sequence alignment of TF DNA-binding domains, and the weblogo and phylogenetic tree based on the alignment, (iv) a TF prediction server to identify new TFs from input sequences and (v) a BLAST server to search against TFs in AnimalTFDB. A new nice web interface was designed for AnimalTFDB 2.0 allowing users to browse and search all data in the database. We aim to maintain the AnimalTFDB as a solid resource for TF identification and studies of transcription regulation and comparative genomics.

  7. Experimental Studies of Toxicity on HNIW and Its Intermediates

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ying; CHEN Shu-sen; JIN Shao-hua; CUI Zhao-kuan

    2006-01-01

    The polycyclic nitramine hexanitrohexaazaisowurtane(HNIW) is a compound of high energy density. HNIW can replace 1, 3, 5-trinitro-1, 3, 5-triazacyclohexane(RDX)or HMX, but its toxicity is unknown. In this paper,HNIW, hexabenzylhexaazaisowurtzitane ( HBIW ), tetraacetyldibenzulhexaazaisowurtzitane ( TADBIW ), tetraacetyldiformylhexaazaisowurtzitane(TADFIW) and tetraacetylhexaazaisowurtzitane(TAIW), which are intermediates of the synthesis of the HNIW, were selected as the tested objects in acute toxicity test, acute eye stimulation test and skin irritation test according to the standards of "chemical product testing method-401: acute oral toxicity test", "chemical product testing means-405: acute eye irritation/corrosion test" and "chemical product testing means-404: acute dermal irritation/corrosion test" of National Circumstance Protect Bureau. The results show that all of the five objects have no toxicity, no stimulation to eye and skin under the tested conditions.

  8. Soil-plant-animal transfer models to improve soil protection guidelines: A case study from Portugal

    NARCIS (Netherlands)

    Rodrigues, S.M.; Pereira, M.E.; Duarte, A.C.; Römkens, P.F.A.M.

    2012-01-01

    Food chain models are essential tools to assess risks of soil contamination in view of product quality including fodder crops and animal products. Here we link soil to plant transfer (SPT) models for potentially toxic elements (PTEs) including As, Ba, Cd, Co, Cu, Hg, Ni, Pb, Sb, U and Zn with models

  9. Epidemiological Study of Animal Leptospirosis in New Caledonia

    Directory of Open Access Journals (Sweden)

    Cédric Roqueplo

    2013-01-01

    Full Text Available Leptospirosis is an important zoonotic disease in the world and a real public health concern for many years in New Caledonia. A cross-sectional survey was carried out on domestic and wild animals from New Caledonia in April 2009. Blood samples were collected from 30 cattle, 29 deers, (Cervus timorensis russa, 25 horses, 51 dogs, and 8 cats and were tested for 23 serovars of pathogenic Leptospira species by the microscopic agglutination test. From the total number of 143 samples, 84 (58.7% were found to be positive towards one or several serovars of pathogenic leptospires. According to the species, the positive sera were obtained from 43% of 30 cattle, 72% of 29 Rusa deer, 80% of 25 horses, and 43% of 51 dogs, and fromall of the 8 cats tested. This study shows the broad dispersion and the high prevalence of the different serogroups of pathogenic Leptospira species tested, particularly among deer and horses. The disease is endemic in domestic animals and concerns all the species.

  10. Nicotine addiction: studies about vulnerability, epigenesis and animal models

    Directory of Open Access Journals (Sweden)

    Bernabeu, Ramon

    2013-07-01

    Full Text Available This article is a summary about the current research of nicotine effects on the nervous system and its relationship to the generation of an addictive behavior. Like other drugs of abuse, nicotine activates the reward pathway, which in turn is involved in certain psychiatric diseases. There are individuals who have a high vulnerability to nicotine addiction. This may be due to genetic and epigenetic factors and/or the environment. In this review, we described some epigenetic factors that may be involved in those phenomena. The two animal models most widely used for studying the reinforcing effects of nicotine are: self-administration and conditioning place preference (CPP. Here, we emphasized the CPP, due to its potential application in humans. In addition, we described the locomotor activity model (as a measure of psychostimulant effects to study vulnerability to drugs of abuse

  11. Improvement of Large Animal Model for Studying Osteoporosis

    Directory of Open Access Journals (Sweden)

    Kiełbowicz Zdzisław

    2015-04-01

    Full Text Available The aim of the study was to determine the impact of steroidal medications on the structure and mechanical properties of supporting tissues of sheep under experimentally-induced osteoporosis. A total of 21 sheep were used, divided into three groups: a negative control (KN (n = 3, a positive control (KP (n = 3 with ovariectomy, and a steroidal group (KS (n = 15 with ovariectomy and glucocorticosteroids. All animals were kept on a low protein and mineral diet and had limited physical activity and access to sunlight. Quantitative computed tomography was the examination method. The declines in the examined parameter values in the KS group were more than three times higher than in the KN group. The study suggests that a glucocorticosteroidal therapy accelerates and intensifies processes taking place in the course of osteoporosis. The combination of glucocorticosteroids with ovariectomy, a restrictive diet, limited physical activity, and no access to sunlight leads to a decrease in radiological bone density.

  12. Studies of Al metabolism in animal by accelerator mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    WangNa-Xiu; ZhuHan-Min; 等

    1997-01-01

    The correlation between Al metabolism and senile dementia in animal has been studied by AMS(accelerator mass spectrometry).Three groups of laboratory rats were fed with normal food.food with high Al content,and with enriched Ca and Mg together with high Al,respectively for six to eight months.Mapping test was made to recored th degree of wisdom degeneration.Half of the rats were sacrificed and Al contents in various organs were measured by atomic absorption spectroscopy.The rest were injected with 26Al,killed after 5,10,15,25,and 35d and 26Al contents measured by AMS.The distribution of Al as well as the correlation among the accumulation of 26Al,and the existed Al content and dementia was studied.

  13. Towards ethically improved animal experimentation in the study of animal reproduction.

    Science.gov (United States)

    Blache, D; Martin, G B; Maloney, S K

    2008-07-01

    The ethics of animal-based research is a continuing area of debate, but ethical research protocols do not prevent scientific progress. In this paper, we argue that our current knowledge of the factors that affect reproductive processes provides researchers with a solid foundation upon which they can conduct more ethical research and simultaneously produce data of higher quality. We support this argument by showing how a deep understanding of the genetics, nutrition and temperament of our experimental animals can improve compliance with two of the '3 Rs', reduction and refinement, simply by offering better control over the variance in our experimental model. The outcome is a better experimental design, on both ethical and scientific grounds.

  14. George Herbert Mead on Humans and Other Animals: Social Relations After Human-Animal Studies

    OpenAIRE

    Rhoda Wilkie; Andrew McKinnon

    2013-01-01

    The turn towards nonhuman animals within sociology has shed a critical light on George Herbert Mead, his apparent prioritisation of language and the anthropocentric focus of Symbolic Interactionism (SI). Although Herbert Blumer canonised Mead as the founder of this perspective he also played a key role in excising the evolutionary and 'more-than-human' components in Mead's work. This intervention not only misrepresented Mead's intellectual project, it also made symbols the predominant concern...

  15. Safety profiling of pioglitazone and telmisartan combination by sub-chronic toxicity study in rat.

    Science.gov (United States)

    Sengupta, Pinaki; Das, Arindam; Ibrahim, Fuzianna; Mandal, Uttam Kumar; Chatterjee, Bappaditya; Mahmood, Syed; Das, Sreemoy Kanti; Kifayatullah, Muhammad

    2016-11-01

    It has been reported that the major cause of mortality in diabetes is cardiovascular diseases and contribution of hypertension is significant in this context. Pioglitazone, a thiazolidinedione class of therapeutic agent is used to treat type 2 diabetes mellitus. Telmisartan, an angiotensin receptor blocker antihypertensive has been reported to have beneficial effect if co-administered with pioglitazone for the management of diabetes complications. The present research work aims to evaluate the safety/toxicity profile of this combination in rat model. The investigation was carried out after co-administering the drugs to the rats for 28 days at three dose levels of 50, 100 and 150 mg/kg covering low to high dose ranges. Various hematological and biochemical parameters were studied in addition to the histopathology of the major organs in order to evaluate the toxicity profile of the combination. Absence of mortality and histopathological changes as well as unaltered hematological and biochemical parameters was observed. This preliminary investigation concludes that the combination of pioglitazone and telmisartan can primarily be stated as safe in animals, even at the dose level which is several folds higher than the intended human dose. Thus, this combination can be explored in future to develop a rational therapy regimen to treat hypertensive diabetic patients.

  16. Toxicity studies of Cordia salicifolia extract Estudo da toxidade do extrato de Cordia salicifolia

    Directory of Open Access Journals (Sweden)

    Roberto Kenji Nakamura Cuman

    2005-03-01

    Full Text Available Este estudo foi realizado para determinar a toxicidade aguda do extrato total de Cordia salicifolia (DL50 após administração oral e intraperitoneal em camundongos, assim como os efeitos do extrato sobre alguns parâmetros bioquímicos no plasma de ratos após um tratamento prolongado (90 dias. A DL50 do extrato administrado por v.o. foi maior que 2000 mg/Kg, enquanto a DL50 por via i.p. foi aproximadamente 920 mg/Kg. A administração oral diária do extrato nas doses de 20, 100, 200 e 400 mg/kg por um período de 90 dias não causou modificações no ganho de peso corporal, no peso dos órgãos, nos parâmetros hematológicos e bioquímicos dos animais. Estes resultados indicam que a administração do extrato por um período mais prolongado não provocou efeitos de toxicidade nos animaisThis study was carried out to determine the acute toxicity of the whole Cordia salicifolia extract (LD50 after oral and intraperitoneal administration in mice, and its effect on certain biochemical parameters in the plasma of rats after 90 days of administration. The oral LD50 value of the extract was higher than 2000 mg/kg while the LD50 by intraperitoneal injections was about 920 mg/kg. A daily oral administration of extracts at 20, 100, 200 and 400 mg/kg doses for 90 days did not cause significant changes in the body weight gain, organs weight or biochemical assays and hematology in the animals. The results showed that the administration of the extract for a prolonged period did not produce toxic effects in the animals

  17. Toxicity studies of Cordia salicifolia extract = Estudo da toxidade do extrato de Cordia salicifolia

    Directory of Open Access Journals (Sweden)

    Silvana Martins Caparroz-Assef

    2005-01-01

    Full Text Available This study was carried out to determine the acute toxicity of the whole Cordia salicifolia extract (LD50 after oral and intraperitoneal administration in mice, and its effect on certainbiochemical parameters in the plasma of rats after 90 days of administration. The oral LD50 value of the extract was higher than 2000 mg/kg while the LD50 by intraperitoneal injections was about 920mg/kg. A daily oral administration of extracts at 20, 100, 200 and 400 mg/kg doses for 90 days did not cause significant changes in the body weight gain, organs weight or biochemical assays and hematology in the animals. The results showed that the administration of the extract for a prolonged period did not produce toxic effects in the animals.Este estudo foi realizado para determinar a toxicidade aguda do extrato total de Cordia salicifolia (DL50 após administração oral e intraperitoneal em camundongos, assim como os efeitos do extrato sobre alguns parâmetros bioquímicos no plasma de ratos após um tratamento prolongado (90 dias. A DL50 do extrato administrado por v.o. foi maior que 2000 mg/Kg, enquanto a DL50 por via i.p. foi aproximadamente 920 mg/Kg. A administração oral diária do extrato nas doses de 20, 100, 200 e 400 mg/kg por um período de 90 dias não causou modificações no ganho de peso corporal, no peso dos órgãos, nosparâmetros hematológicos e bioquímicos dos animais. Estes resultados indicam que a administração do extrato por um período mais prolongado não provocou efeitos de toxicidade nos animais.

  18. Acute toxicity study of Vilocym Premix (herbal growth promoter for Livestockin Wistar Albino Rat

    Directory of Open Access Journals (Sweden)

    A.H. Ahmad

    2009-06-01

    Full Text Available An experimental study with the objective of safety evaluation of Vilocym Premix, herbal growth promoter for Livestock (supplied by Ayurvet Ltd., Baddi, India, was done as per standard guidelines of OECD-423 for acute toxicity testing. Vilocym Premix is a scientifically developed combination of herbs that contains herbal ingredients namely Azadirachta indica, Curcuma longa & many more alongwith natural zeolites. The study was done in 3 males and 3 female Wistar Albino rats, which were administered an initial dose of 50 mg/kg body weight followed by dose rates of 300, 500 & 5000 mg/kg body weight of test compound. The animals were observed for signs of convulsions, tremors, circling, depression, excitement and mortality. Body weight was recorded at 0,7th and 14th day and plasma total protein, albumin; AST and ALT were measured after 3rd day of experiment. No abnormal sign of symptoms were observed in any of the animal fed with Vilocym Premix at the dose rate of 50, 300, 500 & 5000 mg/kg. No mortality was observed indicating safety of herbal premix. [Vet. World 2009; 2(3.000: 100-102

  19. Prenatal developmental toxicity study of ethyl tertiary-butyl ether in rats.

    Science.gov (United States)

    Aso, Sunao; Miyata, Katsumi; Takakura, Saori; Hoshuyama, Satsuki; Muroi, Takako; Kusune, Yuji; Ajimi, Shozo; Furukawa, Kotaro

    2014-01-01

    Ethyl tertiary-butyl ether (ETBE) is commonly used as an oxygenated gasoline additive. In this study, we evaluated its developmental toxicity in rats. ETBE was administered by gavage to 21 or 22 pregnant female Sprague-Dawley rats per group at dose levels of 0, 100, 300 and 1000 mg/kg/day from days 5 through 19 postcoitum to assess its effects on pregnant animals and their embryos and fetuses applied to the OECD testing guideline (no. 414) correspondingly. There were no toxicological effects attributable to ETBE regarding clinical signs, body weight, food intake, necropsy or examination at caesarean section in pregnant animals. There were also no toxicological effects on external, visceral and skeletal examinations of embryos and fetuses. These results indicate that, under the conditions of this study, ETBE had no toxicological effects on pregnant rats or their embryos and fetuses and that the no observed adverse effect level was 1000 mg/kg/day both for pregnant rats and their embryos and fetuses.

  20. Guidance on the selection of cohorts for the extended one-generation reproduction toxicity study (OECD test guideline 443).

    Science.gov (United States)

    Moore, Nigel P; Beekhuijzen, Manon; Boogaard, Peter J; Foreman, Jennifer E; North, Colin M; Palermo, Christine; Schneider, Steffen; Strauss, Volker; van Ravenzwaay, Bennard; Poole, Alan

    2016-10-01

    The extended one-generation reproduction toxicity study (EOGRTS; OECD test guideline 433) is a new and technically complex design to evaluate the putative effects of chemicals on fertility and development, including effects upon the developing nervous and immune systems. In addition to offering a more comprehensive assessment of developmental toxicity, the EOGRTS offers important improvements in animal welfare through reduction and refinement in a modular study design. The challenge to the practitioner is to know how the modular aspects of the study should be triggered on the basis of prior knowledge of a particular chemical, or on earlier findings in the EOGRTS itself, requirements of specific regulatory frameworks notwithstanding. The purpose of this document is to offer guidance on science-based triggers for these extended evaluations.

  1. Epidemiological studies on animal and human trichinellosis in Estonia

    Directory of Open Access Journals (Sweden)

    Järvis T.

    2001-06-01

    Full Text Available From 1992 to 1999, muscle samples from 814 sylvatic animals and 1,173 domestic and synanthropic animals were collected in 15 districts of Estonia ; the prevalence of trichinellosis ranged from 1.0 % to 79.4 % for sylvatic animals and from 0.6 % to 24.5 % for domestic or synanthropic animals and for animals from fur-bearing farms. The most important reservoirs of Trichinella in nature were the raccoon dog, the red fox, the lynx and the wolf. Three species of Trichinella (T. spiralis, T. nativa, and T. britovi were identified by several types of PCR-based analyses. Meat from sylvatic animals was the main source of Trichinella infection for humans.

  2. Antihyperglycemic and subchronic toxicity study of Moringa stenopetala leaves in mice

    Directory of Open Access Journals (Sweden)

    Tesemma Sileshi

    2014-03-01

    Full Text Available Objective: To evaluate the antihyperglycemic activity and subchronic toxicity of an extract of Moringa stenopetala (M. stenopetala leaves in mice. Methods: Antihyperglycemic activities of various solvent subfractions and chromatographic fractions were investigated in alloxan induced diabetic mice. All fractions were administered intragastrically using oral gavage at a dose of 500 mg/kg. For the subchronic toxicity investigation of the 70% ethanol extract of M. stenopetala leaves, a daily dose of 300 or 600 mg/kg body weight was administered to mice over 96 d. Some hematological and plasma biochemical parameters were measured as indices of organ specific toxicity. Preliminary phytochemical screening and antioxidant activity investigation was done using thin layer chromatography method. Results: Among the solvent subfractions of the 70% ethanol extract tested only butanol subfraction exhibited significant reduction of blood glucose level (P<0.05 at 2 h (53.44% and 4.5 h (46.34% in diabetic mice and it was further fractionated chromatographically. This resulted in isolation of three chromatographic fractions (fraction 1, 2, and 3 which exhibited maximal blood glucose reduction (P<0.01 at 6 h (77.2%, at 4.5 h (69.1% and at 4.5 h (71.96% after administration. Furthermore, these fractions exhibited comparable antioxidant activity, and preliminary phytochemical screening indicated the presence of phenolic compounds which may be phenolic glycoside in all fractions. The subchronic toxicity study of the 70% ethanol extract of M. stenopetala leaves revealed that there were no significant differences in body weight, between controls and treated mice. Hematological analysis showed no differences in most parameters examined. Furthermore, it did not significantly affect plasma creatinine, urea, cholesterol, triglycerides and CA125 levels. It also did not significantly affect the plasma T3, T4 and THS level. It, however, caused a significant dose

  3. Multivariate analysis of toxicity experimental results of environmental endpoints. (FutureToxII)

    Science.gov (United States)

    The toxicity of hundreds of chemicals have been assessed in laboratory animal studies through EPA chemical regulation and toxicological research. Currently, over 5000 laboratory animal toxicity studies have been collected in the Toxicity Reference Database (ToxRefDB). In addition...

  4. A review of adverse pregnancy outcomes and formaldehyde exposure in human and animal studies.

    Science.gov (United States)

    Collins, J J; Ness, R; Tyl, R W; Krivanek, N; Esmen, N A; Hall, T A

    2001-08-01

    We examine the potential for reproductive and developmental effects from formaldehyde exposure. Formaldehyde is unlikely to reach the reproductive system in humans in concentrations sufficient to cause damage since it is rapidly metabolized and detoxified upon contact with the respiratory tract. While there are effects seen in in vitro studies or after injection, there is little evidence of reproductive or developmental toxicity in animal studies under exposure levels and routes relevant to humans. Most of the epidemiology studies examined spontaneous abortion and showed some evidence of increased risk (meta-relative risk=1.4, 95% CI 0.9-2.1). We found evidence of reporting biases and publication biases among the epidemiology studies and when these biases were taken into account, we found no evidence of increased risk of spontaneous abortion among workers exposed to formaldehyde (meta-relative risk=0.7, 95% CI 0.5-1.0). The small number of studies on birth defects, low birth weight, and infertility among formaldehyde workers; the limitations in the design of these studies; and the inconsistent findings across these studies make it difficult to draw conclusions from the epidemiology data alone. However, information from experimental studies and studies of metabolism indicate reproductive impacts are unlikely at formaldehyde exposures levels observed in the epidemiology studies.

  5. Quantitative structure-toxicity relationship (QSTR) studies on the organophosphate insecticides.

    Science.gov (United States)

    Can, Alper

    2014-11-04

    Organophosphate insecticides are the most commonly used pesticides in the world. In this study, quantitative structure-toxicity relationship (QSTR) models were derived for estimating the acute oral toxicity of organophosphate insecticides to male rats. The 20 chemicals of the training set and the seven compounds of the external testing set were described by means of using descriptors. Descriptors for lipophilicity, polarity and molecular geometry, as well as quantum chemical descriptors for energy were calculated. Model development to predict toxicity of organophosphate insecticides in different matrices was carried out using multiple linear regression. The model was validated internally and externally. In the present study, QSTR model was used for the first time to understand the inherent relationships between the organophosphate insecticide molecules and their toxicity behavior. Such studies provide mechanistic insight about structure-toxicity relationship and help in the design of less toxic insecticides. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Subchronic Toxicity Study on Soy Isoflavones in Rats1

    Institute of Scientific and Technical Information of China (English)

    WEN-ZHONG ZHANG; WEN-MING CUI; KIN ZHANG; WEI WANG; XU-DONG JIA; XIAO-PENG ZHANG; NING LI

    2009-01-01

    Objective To investigate the subchronic toxicity of soy isoflavones (SIF) in male rats. Method Fifty Sprague-Dawley rats were randomly divided into 5 groups,10 rats per group.SIF were given to rats in different groups by gavage at dose of 0,0.2,0.5,1.5,and 4.5 g/kg bw,respectively for 13 weeks.Clinical manifestations,body weight,and food consumption were observed weekly.At the end of the study,urinalysis,hematology,clinical chemistry,total testosterone,and follicle-stimulating hormone were tested,and histopathological examinations were performed. Results No mortality,ophthalmic abnormalities or treatment-related clinical signs were identified during the study.As compared with the control group,significantly lower body weights and food consumption were observed in 1.5 and 4.5 g/kg bw groups.In clinical chemistry tests,triglyceride was significantly decreased and high-density lipoprotein cholesterol was significantly increased in all SIF-treated groups.Total testosterone levels were significantly lower in 0.50,1.50,and 4.5 g/kg bw dose groups than in the control group.Microscopic examination showed that the mammary glands exhibited hyperplasia and excreted latex in rats of the 4.5 g/kg bw group.No changes attributable to treatment of SIF in other parameters were found. Conclusion SIF at high dosages caused significant endocrine disruption in male rats.The no observed adverse effect level (NOAEL) of SIF to male rats in this study is considered to be 0.20 g/kg bw.

  7. A retrospective study on incidence of lameness in domestic animals

    Directory of Open Access Journals (Sweden)

    A. Mohsina

    2014-08-01

    Full Text Available Aim: To study the incidence of lameness among different species of animals presented to the Veterinary Polyclinic, Indian Veterinary Research Institute, Izatnagar. Materials and Methods: Outpatient department (OPD records for the period from January 2006 to December 2010 were referred and information was collected regarding number of lameness in different species, breeds, type of injury, limb affected, gender, age at onset, treatment offered, outcome and any reoccurrence. In this study, fractured cases were not included. Results: The incidence of lameness among different species were recorded: canine (56%, equine (21%, caprine (7%, feline (3%, cattle (7%, buffalo (5.47%, sheep (0.6%, monkey (0.39% and swine (0.19%. In dog, the different conditions were reported with hind quarter weakness recording 55% of lameness followed by right hind limb lameness (14.7%, left hind limb lameness (12.6%, left forelimb lameness (12%, hip dislocation (6.3% and hip dysplasia (4.2%. In caprines, important causes of lameness were right forelimb lameness (23%, right hind limb lameness (12%, left forelimb lameness (12%, posterior paresis (9%, left shoulder dislocation (14% and right shoulder dislocation (6%. In cattle, 34.28% of cases with right hind limb lameness, 28.5% cases were due to HQW, 14.28% had hip dysplasia, 8.57% suffered left hind limb lameness, 6% cases were recorded with obturator nerve paralysis and 8.57% cases suffered contracted tendon in calves. In buffaloes, cases reported were right carpal arthritis, foot rot and left hind limb lameness (14.28% each, due to bilateral upward luxation of patella and due bilateral purulent wound in stifle (18% each and hip dislocation (21.4%. In equines, lameness were reported with right hind limb affection (13%, left forelimb affection (11%, right forelimb affection (17%, 4% each due to disease of right shoulder, HQW and both forelimb affection, lateral dislocation of patella (3%, affection of both hind limbs (9%, 5

  8. Mechanism underlying the toxic action of molybdenum in the animal organism and the effect of sulfate ion on the course of molybdenum poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Lukashev, A.A.

    1973-01-01

    Oral administration of ammonium molybdate (0.5-50 mg/kg) to rats and rabbits or exposure of the animals to MoO/sub 3/ (7-130 mg/m/sup 3/) for 4 hr significantly decreased the urinary excretion of sulfates, increased the level of free amino acids, and inhibited the activity of alkaline phosphatase in the blood serum, and caused pathomorphological changes in the internal organs. Na sulfate administered orally at 5 or 50 mg sulfate/day to rats and rabbits, resp., increased the Mo and SO/sub 4/ levels in the urine and decreased the symptoms of poisoning. The toxic effects of molybdenum may be due to the formation of thiomolybdates in the organism; sulfates may activate enzymes oxidizing thiomolybdates. 24 references.

  9. Toxicity of a Novel Herbomineral Preparation Las01 on Human Cancer Cell Lines and Its Safety Profile in Humans and Animals

    Directory of Open Access Journals (Sweden)

    Saba Sheikh

    2012-01-01

    Full Text Available Polyhedral formulations based on Rasayana therapy described in Charaka Samhita showed remarkable improvement in quality of life of various cancer patients who have been found to be refractory or poor responders to modern chemotherapy and radiation treatment. One of the most recent novel herbomineral preparation, Las01 prepared absolutely as per the instruction given in the ancient Ayurvedic literature has been found to be effective as a potent anticancer drug in the human cell lines, the MCF-7 and Hela cancer cell lines. This novel preparation of Las01 is also found to be devoid of toxicity both in animals as well as in human subjects, which is the main drawback of chemotherapeutic agents used in modern system of medicine. Our results warrant multicentric clinical trials on a large scale which seems to be a future promising drug to cure incurables cancer patients.

  10. The influence of mechanical loading on osseointegration: an animal study

    Institute of Scientific and Technical Information of China (English)

    FAN YuBo; XIU KaiHua; DONG Xiang; ZHANG Ming

    2009-01-01

    Osseointegration of implant provides a stable support for the prosthesis under functional loads. The timing of loading is a critical parameter that can govern the success of the osseointegration of implant. However, it is not clear whether the early loading can affect the success of osseointegration, or whether the no-loading healing period can be shortened. This paper presents an animal study conducted to investigate how external loads influence the osseointegration at the initial stage of healing. Titanium implants were inserted into the goat tibia laterally, and different axial Ioadings were applied to the im-plants in 4 weeks after surgery. After the 2 weeks period of early loading, animals were sacrificed and the tibia bones with the implants were cut off from the bodies. Then mechanical test was employed to find out the differences in the pull-out force, and shear strength at the bone-implant interface between the non-loaded and the loaded implants. The implant-bone interfaces were analyzed by histomor-phometric method, SEM (scanning electron micrograph) and EDS (energy density spectrum). The re-sults indicated that the bone-implant interface did not well integrate 4 weeks after surgery, and the fi-brous tissue could be found at the interfaces of the specimens without Ioadings. While the results of loaded specimens with 10 N axial force showed that that parts of the interface were well integrated, indicating that the early mild loading may play a positive role in the process of the osseointegration. The results support that a certain range of external loading would influence the process of osseointe, gration, and appropriate mechanical loading can be applied to shorten the osseointegration period after surgery.

  11. Graphics and Animation as Instructional Tools: A Case Study.

    Science.gov (United States)

    Peters, H. J.; Daiker, K. C.

    1982-01-01

    Investigated the overall effectiveness of and use of animation/graphics in "Introduction to Organic Chemistry" computer programs on student achievement and attitudes (n=approximately 400). Results indicate that although materials were effective animation sequences, they did not have an effect on student test scores. (JN)

  12. Animal Rights: Selected Resources and Suggestions for Further Study.

    Science.gov (United States)

    Davidoff, Donald J.

    1989-01-01

    Presents an annotated list of selected resources intended to serve as a guide to the growing amount of material on animal rights. Suggestions to aid in additional research include subject headings used to find books, indexes used to locate periodical articles, sources for locating organizations, and a selected list of animal rights organizations.…

  13. Pulmonary toxicity of nanomaterials: a critical comparison of published in vitro assays and in vivo inhalation or instillation studies.

    Science.gov (United States)

    Landsiedel, Robert; Sauer, Ursula G; Ma-Hock, Lan; Schnekenburger, Jürgen; Wiemann, Martin

    2014-11-01

    To date, guidance on how to incorporate in vitro assays into integrated approaches for testing and assessment of nanomaterials is unavailable. In addressing this shortage, this review compares data from in vitro studies to results from in vivo inhalation or intratracheal instillation studies. Globular nanomaterials (ion-shedding silver and zinc oxide, poorly soluble titanium dioxide and cerium dioxide, and partly soluble amorphous silicon dioxide) and nanomaterials with higher aspect ratios (multiwalled carbon nanotubes) were assessed focusing on the Organisation for Economic Co-Operation and Development (OECD) reference nanomaterials for these substances. If in vitro assays are performed with dosages that reflect effective in vivo dosages, the mechanisms of nanomaterial toxicity can be assessed. In early tiers of integrated approaches for testing and assessment, knowledge on mechanisms of toxicity serves to group nanomaterials thereby reducing the need for animal testing.

  14. Polyethylene glycol-g-polyvinyl alcohol grafted copolymer: reproductive toxicity study in Wistar rats.

    Science.gov (United States)

    Heuschmid, Franziska F; Schneider, Steffen; Schuster, Paul; Lauer, Birthe; van Ravenzwaay, Bennard

    2013-07-01

    Polyethylene glycol-g-polyvinyl alcohol (PEG-PVA) grafted copolymer was administered by gavage to groups of 25 male and 25 female young Wistar rats at doses of 0 (vehicle control), 100, 300, or 1000 mg/kg bw/day for one generation (F0). The study followed the treated F0 generation through mating, gestation, lactation, and weaning of the F1 generation. F1 animals were mated and followed to gestation day (GD) 15-17 at which time F2 implants were evaluated. There were no indications from the various clinical and gross pathological examinations that the oral administration of PEG-PVA grafted copolymer to the F0-parental rats produced any signs of general, reproductive, or developmental toxicity in the F0 or F1 animals or F2 implants. Based on the lack of any dose-related or biologically relevant effects on fertility, reproduction, development, and overall health of rats gavaged with PEG-PVA grafted copolymer and their progeny, the no-observed-adverse effect level (NOAEL) was determined to be the highest dose tested of 1000 mg/kg bw/day.

  15. Toxic proteins in plants.

    Science.gov (United States)

    Dang, Liuyi; Van Damme, Els J M

    2015-09-01

    Plants have evolved to synthesize a variety of noxious compounds to cope with unfavorable circumstances, among which a large group of toxic proteins that play a critical role in plant defense against predators and microbes. Up to now, a wide range of harmful proteins have been discovered in different plants, including lectins, ribosome-inactivating proteins, protease inhibitors, ureases, arcelins, antimicrobial peptides and pore-forming toxins. To fulfill their role in plant defense, these proteins exhibit various degrees of toxicity towards animals, insects, bacteria or fungi. Numerous studies have been carried out to investigate the toxic effects and mode of action of these plant proteins in order to explore their possible applications. Indeed, because of their biological activities, toxic plant proteins are also considered as potentially useful tools in crop protection and in biomedical applications, such as cancer treatment. Genes encoding toxic plant proteins have been introduced into crop genomes using genetic engineering technology in order to increase the plant's resistance against pathogens and diseases. Despite the availability of ample information on toxic plant proteins, very few publications have attempted to summarize the research progress made during the last decades. This review focuses on the diversity of toxic plant proteins in view of their toxicity as well as their mode of action. Furthermore, an outlook towards the biological role(s) of these proteins and their potential applications is discussed.

  16. A review of implications of antiquality and toxic components in unconventional feedstuffs advocated for use in intensive animal production in Nigeria.

    Science.gov (United States)

    Aregheore, E M

    1998-02-01

    There are a number of unconventional feed resources in Nigeria. Most are rich sources of plant protein. Since protein is the most expensive and limiting nutrient in tropical livestock nutrition, these unconventional feed resources may fill a gap in protein deficiency. However, most contain antiquality and toxic components which make them unsafe as protein and carbohydrate sources in livestock nutrition. The presence of saponins, lectins, tannins, trypsin inhibitors, cyanogenic glucoside and others in African locust bean meal (Parkia filicoidea Welw), avocado seed meal (Persea americana), bambara groundnut meal (Voandzeia subterranea), cocoa by-product meal (Theobroma coca), coffee pulp meal (Coffee arabica), mango seed kernel meal (Mangifera indica), rubber seed meal (Hevea brasiliensis), sesame seed (Sesamum indicum L) and shear-butter cake (Vitellaria paradoxa, G) are not uncommon and make rations prepared with them unpalatable and unacceptable to animals. They also interfere with nutrient bioavailability and utilization. Drying, soaking, leaching and fermentation are simple means of detoxifying these feed sources to reduce the presence of antiquality and toxic components.

  17. Comparative studies on plasma mineral status of cattle in fluoride toxic brackish water zone of Punjab, India

    Directory of Open Access Journals (Sweden)

    Sushma Chhabra

    2012-05-01

    Full Text Available Objective: Chronic fluoride intoxication or fluorosis is a worldwide health problem in humans and animals. The present research work was aimed to assess the status of copper, zinc, cobalt, manganese, magnesium, calcium and phosphorus in blood of fluorotic cattle in brackish water zone of Punjab. Methods: The present study was conducted in villages of district Muktsar, a brackish water zone, of Punjab state. Cattle (n=103 showing signs of dental lesions or lameness, from the villages with water fluoride concentration more than 1 ppm, were selected for the study whereas cattle (n=98 from villages with water fluoride concentration less than 1 ppm and with no clinical signs served as control. Blood samples were collected from both the groups and were analysed for minerals.Results: Significantly (P<0.05 higher plasma F concentrations were observed in animals of fluorotic region in comparison to healthy control animals. Concentrations of plasma Ca, Mg, Cu and Zn were significantly lower in cattle of hydrofluorotic region. Plasma phosphorus, iron and iodine concentrations were higher in animals of hydrofluorotic region whereas Mo and Mn did not differ between the two groups. Conclusions: Present study indicated decrease in certain essential minerals in animals of fluorotic region and such changes may contribute to the toxic effects associated with exposure to excess fluoride and salinity

  18. Toxicological study of plant extracts on termite and laboratory animals.

    Science.gov (United States)

    Rahman, I; Gogoi, Inee; Dolui, A K; Handique, Ruma

    2005-04-01

    Toxic activity of leaf extracts of Polygonum hydropiper L. and Pogostemon parviflorus Benth. were tested in the laboratory against tea termite, Odontotermes assamensis Holm. Both the tested extracts caused mortality of the termite. The highest toxic activity (100%) was found in the 2.0% chloroform extracts of P. hydropiper. The chloroform extract of P. hydropiper was explored for possible mammalian toxicological effects. The LD50 was 758.58 mg/kg in male albino mice. Subcutaneous injection of sub-lethal dose of extract into male mice once a week for 6 weeks failed to express any significant influence on WBC, RBC count and blood cholesterol.

  19. Postoperative pain management and proinflammatory cytokines: animal and human studies.

    Science.gov (United States)

    Shavit, Yehuda; Fridel, Keren; Beilin, Benzion

    2006-12-01

    The postoperative period is associated with neuroendocrine, metabolic, and immune alterations, which are the combined result of tissue damage, anesthesia, postoperative pain, and psychological stress. Limited evidence indicates that pain management in the postoperative period can affect the outcome of the surgery, reducing cardiac, pulmonary, and metabolic complications. Recent evidence indicates that pain and immune factors, especially proinflammatory cytokines, mutually interact and influence each other. A series of animal studies demonstrates that effective preemptive analgesia improved postoperative recovery, and this effect was enhanced by coadministration of IL-1ra together with the preemptive analgesics. Furthermore, preemptive analgesia attenuated surgery-induced PGE(2) production in the amygdala and the activation of the HPA axis. IL-1 signaling is required for the production of amygdala PGE(2) in response to surgical stress, and may thus affect the physiological and psychological aspects of surgical stress. These reports suggest that short-term effective analgesia can have long-lasting beneficial effects on surgery recovery. They further suggest that IL-1 blockade should be considered in the clinical management of pain associated with peripheral or nerve injury. Another series of human studies describes an interaction between the effectiveness of postoperative pain relief and surgery-associated immune alterations: In three separate studies, the more effective pain management technique was associated with diminished surgery-induced immune alterations, especially diminished elevation of IL-1. Reduced elevation of postoperative IL-1 and effective pain relief may both contribute to an attenuated illness response and a better surgery outcome.

  20. Acute toxicity study of a simian immunodeficiency virus-based lentiviral vector for retinal gene transfer in nonhuman primates.

    Science.gov (United States)

    Ikeda, Yasuhiro; Yonemitsu, Yoshikazu; Miyazaki, Masanori; Kohno, Ri-ichiro; Murakami, Yusuke; Murata, Toshinori; Goto, Yoshinobu; Tabata, Toshiaki; Ueda, Yasuji; Ono, Fumiko; Suzuki, Toshimichi; Ageyama, Naohide; Terao, Keiji; Hasegawa, Mamoru; Sueishi, Katsuo; Ishibashi, Tatsuro

    2009-09-01

    A phase 1 clinical trial evaluating the safety of gene therapy for patients with wet age-related macular degeneration (AMD) or retinoblastoma has been completed without problems. The efficacy of gene therapy for Leber's congenital amaurosis (LCA) was reported by three groups. Gene therapy may thus hold promise as a therapeutic method for the treatment of intractable ocular diseases. However, it will first be important to precisely evaluate the efficiency and safety of alternative gene transfer vectors in a preclinical study using large animals. In the present study, we evaluated the acute local (ophthalmic) and systemic toxicity of our simian immunodeficiency virus from African green monkeys (SIVagm)-based lentiviral vectors carrying human pigment epithelium-derived factor (SIV-hPEDF) for transferring genes into nonhuman primate retinas. Transient inflammation and elevation of intraocular pressure were observed in some animals, but these effects were not dose dependent. Electroretinograms (ERGs), including multifocal ERGs, revealed no remarkable change in retinal function. Histopathologically, SIV-hPEDF administration resulted in a certain degree of inflammatory reaction and no apparent structural destruction in retinal tissue. Regarding systemic toxicity, none of the animals died, and none showed any serious side effects during the experimental course. No vector leakage was detected in serum or urine samples. We thus propose that SIVagm-mediated stable gene transfer might be useful and safe for ocular gene transfer in a clinical setting.

  1. Toxicity of dioxin to developing teeth and salivary glands : An experimental study

    OpenAIRE

    2006-01-01

    Dioxins are ubiquitous environmental poisons having unequivocal adverse health effects on various species. The majority of their effects are thought to be mediated by the aryl hydrocarbon receptor (AhR). Developing human teeth may be sensitive to dioxins and the most toxic dioxin congener, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is developmentally toxic to rodent teeth. Mechanisms of TCDD toxicity can be studied only experimentally. The aim of the present thesis work was to delineate...

  2. Galenics: studies of the toxicity and distribution of sugar substitutes on Apis mellifera

    OpenAIRE

    RADEMACHER, Eva; Fahlberg, Anja; Raddatz, Marlene; Schneider, Saskia; Voigt, Kathrin

    2013-01-01

    International audience; The aim of this study was to find a substitute to sugar water in medicinal treatments of honey bee colonies with the same properties but without being ingested by bees or being toxic to them. Tylose MH, sorbitol and glycerol were tested for their attractiveness to Apis mellifera, their application ability, toxicity via individual application and distribution in small groups respectively a small colony. Neither of the substances proved attractive or toxic. All had good ...

  3. Chronic toxicity and carcinogenicity study of erythritol in rats

    NARCIS (Netherlands)

    Lina, B.A.R.; Bos-Kuijpers, M.H.M.; Til, H.P.; Bär, A.

    1996-01-01

    The potential toxicity and carcinogenicity of erythritol, a low-calorie sugar substitute, were examined in Wistar Crl:(WI) WU BR rats. Groups of 50 rats of each sex consumed diets with 0, 2, 5, or 10% erythritol, or 10% mannitol, for a period of 104-107 weeks. To each of these main groups, two

  4. Toxicity Evaluation of Engineered Nanomaterials (Phase 1 Studies)

    Science.gov (United States)

    2012-01-01

    Physiol. Rev. 2007 87, 315-424. [22] Monte M.; Benetti R.; Buscemi G.; Sandy P.; Del Sal G.; and Schneider C.. The Cell Cycle- regulated Protein...Dosimetry Considerations for In Vitro Nanoparticle Toxicity Assessments. Toxicol. Sci. 2007, 95, 300–312. [34] Feng, Q.; Li, P.; Salamanca , C

  5. Subchronic Inhalation Toxicity Study of n-pentane in Rats

    Directory of Open Access Journals (Sweden)

    Jong-Kyu Kim

    2012-09-01

    Conclusion: The no-observable-adverse-effect level (NOAEL of n-pentane is evaluated as being more than 6,885 ppm (20.3 mg/L in both male and female rats. n-pentane was not a classified specific target organ toxicity in the globally harmonized classification system (GHS.

  6. Acute and subchronic toxicity studies of kernel extract of Sclerocarya ...

    African Journals Online (AJOL)

    Administrator

    evaluation was done by oral feeding of the rats with the seed kernel extract daily at doses .... Significantly different from the control (P < 0.05) using one way analysis of variance. Subchronic ... acute toxicity did not produce any grossly negative behavioural changes such .... against garlic-induced oxidative stress. Journal of ...

  7. Acute toxicity studies of aqueous stem bark extract of Ximenia ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-05-16

    May 16, 2008 ... African Journal of Biotechnology Vol. 7 (10), pp. ... Full Length Research Paper ... histopathological examination did not show any significant (P<0.05) damage as a result of the extract ... that the fruits contain hydrocyanic acid which is toxic. .... lesions in the organs could suggest the level of safety of.

  8. Thallium Toxicity: The Problem; An Analytical Approach; An Antidotal Study

    Science.gov (United States)

    1993-05-15

    Possible toxic mechanisms of T1 include ligand formation with protein sulfhydryl groups, inhibition of cellular respiration, interaction with riboflavin ...and riboflavin -based cofactors, and disruption of calcium homeostasis. The principal clinical features of thallotoxicosis are gastroenteritis...anticorrosive), optical lenses (increases refractive index), low-temperature thermometers, dye and pigments (artist paints), semiconduc- tors, superconducting

  9. EVALUATION OF ACUTE TOXICITY STUDY AND DIURETIC ACTIVITY OF URAL SYRUP

    Directory of Open Access Journals (Sweden)

    Thakkar Tejas

    2013-08-01

    Full Text Available There are considerable amount of scientific evidences available for diuretic activity of individual ingredients of a polyherbal formulation Ural Syrup however no evidence has been found which proves overall safety and efficacy of the formulation. The present study was undertaken to investigate safety as well as Diuretic activity of this polyherbal formulation- Ural Syrup. Acute toxicity study was carried out as per OECD Guideline 420. The Ural syrup (1.8mL/kg and 3.6mL/kg was tested for its diuretic activity on rat model. Hydrochlorothiazide (HCTZ (10mg/kg was used as positive control in study. The diuretic effect of the Ural syrup was evaluated by measuring urine volume, pH and excretion of sodium and potassium content. In result, significant increase in urine volume was observed at both dosage levels of Ural syrup in comparison to normal control group. There was no significant change observed in pH of urine. The excretion of Sodium was also found significantly increased at both dosage levels but more in TEDx2 group with respect to TED group. Potassium excretion was found increased only at TEDx2 group as compared to normal control group. It can be concluded that Ural syrup produced considerable diuretic effect which appeared to be comparable to that produced by the reference diuretic HCTZ. There was no lethality and toxic reaction found among the tested animals. The present study provides scientific support that Ural syrup can be employed as a safe and effective diuretic drug.

  10. Study on Dynamic Information of Animal Genetic Resources in China

    Institute of Scientific and Technical Information of China (English)

    MA Yue-hui; XU Gui-fang; WANG Duan-yun; LIU Hai-liang; YANG Yan

    2003-01-01

    The dynamic information of 331 animal genetic resources in 17 important animal genetic re-source provinces (regions) was analyzed. According to the population inbreeding coefficient, combiningwith the information of population dynamic change trend and cross degree, these genetic resources forthreatened degrees were classified. The results indicated that the population size of 138 breeds had in-creased, 147 breeds had decreased, 3 breeds were constant, 7 breeds (or varieties) were extinct, 9 breeds(or varieties) were critically endangered and needed urgently conserve, 50 breeds (or varieties) were endan-gered and should be conserved. We put forward a conservation and utilization plan for animal genetic re-sources.

  11. Genetic and ecological studies of animals in Chernobyl and Fukushima.

    Science.gov (United States)

    Mousseau, Timothy A; Møller, Anders P

    2014-01-01

    Recent advances in genetic and ecological studies of wild animal populations in Chernobyl and Fukushima have demonstrated significant genetic, physiological, developmental, and fitness effects stemming from exposure to radioactive contaminants. The few genetic studies that have been conducted in Chernobyl generally show elevated rates of genetic damage and mutation rates. All major taxonomic groups investigated (i.e., birds, bees, butterflies, grasshoppers, dragonflies, spiders, mammals) displayed reduced population sizes in highly radioactive parts of the Chernobyl Exclusion Zone. In Fukushima, population censuses of birds, butterflies, and cicadas suggested that abundances were negatively impacted by exposure to radioactive contaminants, while other groups (e.g., dragonflies, grasshoppers, bees, spiders) showed no significant declines, at least during the first summer following the disaster. Insufficient information exists for groups other than insects and birds to assess effects on life history at this time. The differences observed between Fukushima and Chernobyl may reflect the different times of exposure and the significance of multigenerational mutation accumulation in Chernobyl compared to Fukushima. There was considerable variation among taxa in their apparent sensitivity to radiation and this reflects in part life history, physiology, behavior, and evolutionary history. Interestingly, for birds, population declines in Chernobyl can be predicted by historical mitochondrial DNA base-pair substitution rates that may reflect intrinsic DNA repair ability. © The American Genetic Association 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Toxicity of formaldehyde and acrolein mixtures : in vitro studies using nasal epithelial cells

    NARCIS (Netherlands)

    Cassee, F.R.; Stenhuis, W.S.; Groten, J.P.; Feron, V.J.

    1996-01-01

    In vitro studies with human and rat nasal epithelial cells were carried out to investigate the combined toxicity of formaldehyde and acrolein and the role of aldehyde dehydrogenases in this process. These studies showed that the toxic effect of mixtures of aldehydes was additive. In addition, aldehy

  13. Dermal toxicity studies of technical polychlorinated biphenyls and fractions thereof in rabbits

    NARCIS (Netherlands)

    Vos, J.G.; Beems, R.B.

    1971-01-01

    A significant difference in toxicity between 3 polychlorinated biphenyl (PCB) preparations was found in a prior study: Clophen A 60 and Phenoclor DP6 showing the highest, Aroclor 1260 the lowest, toxicity (Vos and Koeman, 1970). A subsequent study revealed the presence of tetra- and pentachlorodiben

  14. The role of body-on-a-chip devices in drug and toxicity studies.

    Science.gov (United States)

    Esch, M B; King, T L; Shuler, M L

    2011-08-15

    High-quality, in vitro screening tools are essential in identifying promising compounds during drug development. Tests with currently used cell-based assays provide an indication of a compound's potential therapeutic benefits to the target tissue, but not to the whole body. Data obtained with animal models often cannot be extrapolated to humans. Multicompartment microfluidic-based devices, particularly those that are physical representations of physiologically based pharmacokinetic (PBPK) models, may contribute to improving the drug development process. These scaled-down devices, termed micro cell culture analogs (μCCAs) or body-on-a-chip devices, can simulate multitissue interactions under near-physiological fluid flow conditions and with realistic tissue-to-tissue size ratios. Because the device can be used with both animal and human cells, it can facilitate cross-species extrapolation. Used in conjunction with PBPK models, the devices permit an estimation of effective concentrations that can be used for studies with animal models or predict the human response. The devices also provide a means for relatively high-throughput screening of drug combinations and, when utilized with a patient's tissue sample, an opportunity for individualized medicine. Here we review efforts made toward the development of microfabricated cell culture systems and give examples that demonstrate their potential use in drug development, such as identifying synergistic drug interactions as well as simulating multiorgan metabolic interactions. In addition to their use in drug development, the devices also can be used to estimate the toxicity of chemicals as occupational hazards and environmental contaminants.

  15. Applications of stable isotopes to study plant-animal relationships in terrestrial ecosystems

    Institute of Scientific and Technical Information of China (English)

    WANG Jianzhu; LIN Guanghui; HUANG Jianhui; HAN Xingguo

    2004-01-01

    As natural tracers, stable isotopes have been extensively used in plant physiological, ecological and environmental research. Recently, animal physiological ecologists have also applied stable isotope techniques to study plant- animal relationships. The isotopic compositions of animal body generally reflect and integrate their diets over a time period ranging from hours to years to the lifetime of an individual. When animal living habitat changes or animals move to a new environment, the animal isotopic compositions will shift accordingly. Thus, stable isotope signatures of an animal can truly reflect its food sources, habitat, distribution and movement patterns during a given time period. Moreover, by analyzing animal-tissue isotopic compositions at different temporal scales, we can improve our understanding of animal adaptation to environmental changes. Stable isotope technique also provides an ideal tool to study animal foodweb relationship and community structure because of isotopic fractionation during the processes of nutrient assimilation by animals. Stable isotope technique can continuously measure animal trophic position in a foodweb, which can eventually reveal the predator-prey relationship and its role in determining matter balance and energy flow in the entire ecosystem. Stable isotope technique has been one of the most important and efficient tools in studying plant-animal relationship. In this paper, we first review recent advances in the application of stable isotope techniques to plant-animal relationship research then evaluate their advantages and disadvantages, and finally discuss some future directions associated with stable isotope applications to plant-animal relationship research.

  16. Acute and subchronic toxicity study of the water extract from dried fruits of Piper nigrum L. in rats

    Directory of Open Access Journals (Sweden)

    Kanjana Jaijoy

    2007-03-01

    Full Text Available The study was carried out to evaluate acute and subchronic toxicities of the water extract from the dried fruits of Piper nigrum L. A single oral administration of the extract at a dose of 5,000 mg/kg body weight (5 male, 5 female did not produce signs of toxicity, behavioral changes, mortality, changes on gross appearance or histopathological changes of internal organs. The subchronic toxicity was determined by oral feeding both male and female rats (10 male, 10 female daily with the test substance at the doses of 300, 600 and 1,200 mg/kg body weight continuously for 90 days. The examinations of signs, animal behavior and health monitoring showed no abnormalities in the test groups as compared to the controls. The test and control groups (on the 90th day and the satellite group (on the 118th day were analyzed by measuring their final body and organ weights, taking necropsy, and examining hematology, blood clinical chemistry and histopathology. The results suggest that the water extract from the dried fruits of P. nigrum does not cause acute or subchronic toxicities in either male or female rats.

  17. (1)H NMR based metabolomics approach to study the toxic effects of herbicide butachlor on goldfish (Carassius auratus).

    Science.gov (United States)

    Xu, Hua-Dong; Wang, Jun-Song; Li, Ming-Hui; Liu, Yan; Chen, Ting; Jia, Ai-Qun

    2015-02-01

    Butachlor, one of the most widely used herbicides in agriculture, has been reported with high ecotoxicity to aquatic plants and animals. In this study, a (1)H NMR based metabolomics approach combined with histopathological examination and biochemical assays was applied to comprehensively investigate the toxic effects of butachlor on four important organs (gill, brain, liver and kidney) of goldfish (Carassius auratus) for the first time. After 10 days' butachlor exposure at two dosages of 3.2 and 0.64 μmol/L, fish tissues (gill, brain, liver and kidney) and serum were collected. Histopathological inspection revealed severe impairment of gill filaments and obvious cellular edema in livers and kidneys. The increase of glutathione peroxidase (GSH-Px) activity in gill and methane dicarboxylic aldehyde (MDA) level in four tissues reflected the disturbance of antioxidative system in the intoxicated goldfish. Serum lactate dehydrogenase (LDH) activity and creatinine (CRE) level were increased in butachlor exposure groups, suggesting liver and kidney injuries induced by butachlor. Orthogonal signal correction partial least-squares discriminant analysis (OSC-PLS-DA) of NMR profiles disclosed metabolic changes that were related to the toxic effects of butachlor including oxidative stress, disorder of energy metabolism and amino acids metabolism, and disturbance of neurotransmitter balance in butachlor exposed goldfish. This integrated metabolomics approach provided a molecular basis underlying the toxicity of butachlor and demonstrated that metabolomics was a powerful and highly effective approach to elucidate the toxicity and underlying mechanisms of herbicides and pesticides, applicable for their risk assessment.

  18. Acute and subchronic toxicity study of the water extract from root of Citrus aurantifolia (Christm. et Panz. Swingle in rats

    Directory of Open Access Journals (Sweden)

    Kanjana Jaijoy

    2007-03-01

    Full Text Available Acute and subchronic toxicities of the water extract from the roots of Citrus aurantifolia were studied in both male and female rats. Oral administration of the extract at a single dose of 5,000 mg/kg body weight (5 male, 5 female did not produce signs of toxicity, behavioral changes, mortality or differences on gross appearance of internal organs. The subchronic toxicity was determined by oral feeding the test substance at the doses of 300, 600 and 1,200 mg/kg body weight for 90 days (10 male, 10 female. The examinations of signs, animal behavior and health monitoring showed no signs of abnormalities in the test groups as compared to the controls. The test and control groups (on the 90th day and the satellite group (on the 118th day were analyzed by measuring their final body and organ weights, taking necropsy, and examining hematological parameters, blood clinical chemistry and histopathology features. The oral administration of 1,200 mg/kg/ day of the extract of C. aurantifolia in male and female rats caused a significant increase in the liver enzymes, which remained within the normal range, but did not produce a significant histopathological change in the internal organs. In conclusion, the extract from the roots of C. aurantifolia administered orally did not cause acute or subchronic toxicities to male and female rats.

  19. An animal model to study health effects during continuous low-dose exposure to the nerve agent VX.

    Science.gov (United States)

    Rocksén, David; Elfsmark, Daniel; Heldestad, Victoria; Wallgren, Karin; Cassel, Gudrun; Göransson Nyberg, Ann

    2008-08-19

    In the present study, we have developed an animal model to study long-term health effects of continuous exposure of toxic chemical agents, in awake, freely moving rats. The aim was to evaluate the effect of low-dose exposure of the nerve agent VX, and to find specific biomarkers for intoxication. To exclude the influence of stress, we used an implanted radio-telemetric device for online registration of physiological parameters, and an osmotic pump, implanted subcutaneously, for continuous exposure of the toxic agent. Our results showed that the lowest observable effect dose of VX in Wistar rats was 5 microg/kg/24 h, after continuous exposure by the osmotic pump. Although we observed significant inhibition of acetylcholinesterase (AChE) in blood and a significant decrease in body weight gain at this dose, no change in blood pressure, heart rate or respiratory rate was registered. However, a significant decrease in the thyroid hormone, free T4, was measured in blood after 8 weeks, indicating that low doses of VX might affect the thyroid function. Rats given repeated daily injections were more sensitive to VX and needed only 1/10 of the concentration to reach a similar level of AChE inhibition, compared to animals exposed by the osmotic pump. Moreover, the results showed that exposure of VX in our experimental design, does not induce an increase in corticosterone blood levels. Thus, the model used in this investigation renders minimal stress and will not cause unnecessary pain to the animals, indicating that this model could be a useful tool to study long-term effects of various toxic substances in freely moving rats.

  20. Animal models for the study of arterial hypertension

    Indian Academy of Sciences (India)

    Waleska C Dornas; Marcelo E Silva

    2011-09-01

    Hypertension is one of the leading causes of disability or death due to stroke, heart attack and kidney failure. Because the etiology of essential hypertension is not known and may be multifactorial, the use of experimental animal models has provided valuable information regarding many aspects of the disease, which include etiology, pathophysiology, complications and treatment. The models of hypertension are various, and in this review, we provide a brief overview of the most widely used animal models, their features and their importance.

  1. Preliminary phytochemical,acute oral toxicity and antihepatotoxic study of roots of Paeonia officinalis Linn.

    Institute of Scientific and Technical Information of China (English)

    Feroz; Ahmad; Nahida; Tabassum

    2013-01-01

    Objective:To carry out a preliminary phytochemical,acute oral toxicity and antihepatotoxic study of the roots of Paeonia officinalis(P.officinalis)L.Methods:Preliminary phytochemical investigation was done as per standard procedures.Acute oral toxicity study was conducted as per OECD 425 guidelines.The antihepatotoxic activity of aqueous extract of root of P.officinalis was evaluated against carbon tetrachloride(CCl4)induced hepatic damage in rats.Aqueous extract of P.officinalis at the dose levels of 100 and 200 mg/kg body weight was administered daily for 14 d in experimental animals.Liver injury was induced chemically,by CCl4 administration(1 mL/kg i.p.).The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase(AST),alanine aminotransferase(ALT),serum alkaline phosphatase(SALP),total bilirubin and total protein(TP)along with histopathological studies.Result:Phytochemical screening revealed that the roots of P.officinalis contain alkaloids,tannins,saponins,glycosides,carbohydrates,flavonoids,terpenes,steroids and proteins.The aqueous extract did not cause any mortality up to 2000 mg/kg.In rats that had received the root extract at the dose of 100 and 200 mg/kg,the substantially elevated AST,ALT,SALP,total bilirubin levels were significantly lowered,respectively,in a dose dependent manner,along with CCl4 while TP levels were elevated in these groups.Histopathology revealed regeneration of the livers in extract treated groups while Silymarin treated rats were almost normal.Conclusions:The aqueous extract of P.officinalis is safe and possesses antihepatotoxic potential.

  2. ANIMAL MODELS FOR THE STUDY OF LEISHMANIASIS IMMUNOLOGY

    Directory of Open Access Journals (Sweden)

    Elsy Nalleli Loria-Cervera

    2014-01-01

    Full Text Available Leishmaniasis remains a major public health problem worldwide and is classified as Category I by the TDR/WHO, mainly due to the absence of control. Many experimental models like rodents, dogs and monkeys have been developed, each with specific features, in order to characterize the immune response to Leishmania species, but none reproduces the pathology observed in human disease. Conflicting data may arise in part because different parasite strains or species are being examined, different tissue targets (mice footpad, ear, or base of tail are being infected, and different numbers (“low” 1×102 and “high” 1×106 of metacyclic promastigotes have been inoculated. Recently, new approaches have been proposed to provide more meaningful data regarding the host response and pathogenesis that parallels human disease. The use of sand fly saliva and low numbers of parasites in experimental infections has led to mimic natural transmission and find new molecules and immune mechanisms which should be considered when designing vaccines and control strategies. Moreover, the use of wild rodents as experimental models has been proposed as a good alternative for studying the host-pathogen relationships and for testing candidate vaccines. To date, using natural reservoirs to study Leishmania infection has been challenging because immunologic reagents for use in wild rodents are lacking. This review discusses the principal immunological findings against Leishmania infection in different animal models highlighting the importance of using experimental conditions similar to natural transmission and reservoir species as experimental models to study the immunopathology of the disease.

  3. Gene expression profiling of MPP+-treated MN9D cells: a mechanism of toxicity study.

    Science.gov (United States)

    Wang, Jianyong; Xu, Zengjun; Fang, Hong; Duhart, Helen M; Patterson, Tucker A; Ali, Syed F

    2007-09-01

    Parkinson's disease (PD) is a common neurodegenerative disease characterized by progressive loss of midbrain dopaminergic neurons with unknown etiology. MPP+ (1-methyl-4-phenylpyridinium) is the active metabolite of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which induces Parkinson's-like syndromes in humans and animals. MPTP/MPP+ treatment produces selective dopaminergic neuronal degeneration, therefore, these agents are commonly used to study the pathogenesis of PD. However, the mechanisms of their toxicity have not been elucidated. In order to gain insights into MPP+-induced neurotoxicity, a gene expression microarray study was performed using a midbrain-derived dopaminergic neuronal cell line, MN9D. Utilizing a two-color reference design, Agilent mouse oligonucleotide microarrays were used to examine relative gene expression changes in MN9D cells treated with 40microM MPP+ compared with controls. Bioinformatics tools were used for data evaluation. Briefly, raw data were imported into the NCTR ArrayTrack database, normalized using a Lowess method and data quality was assessed. The Student's t-test was used to determine significant changes in gene expression (set as p1.5). Gene Ontology for Function Analysis (GOFFA) and Ingenuity Pathway Analysis were employed to analyze the functions and roles of significant genes in biological processes. Of the 51 significant genes identified, 44 were present in the GOFFA or Ingenuity database. These data indicate that multiple pathways are involved in the underlying mechanisms of MPP+-induced neurotoxicity, including apoptosis, oxidative stress, iron binding, cellular metabolism, and signal transduction. These data also indicate that MPP+-induced toxicity shares common molecular mechanisms with the pathogenesis of PD and further pathway analyses will be conducted to explore these mechanisms.

  4. Optimization of an animal test protocol for toxicogenomics studies (ii); a cross-laboratory gene expression analysis.

    Science.gov (United States)

    Sumida, Kayo; Saito, Koichi; Oeda, Kenji; Otsuka, Masanori; Tsujimura, Kazunari; Miyaura, Hideki; Sekijima, Masaru; Nakayama, Koji; Kawano, Yukiko; Kawakami, Yuki; Asamoto, Makoto; Shirai, Tomoyuki

    2007-02-01

    Toxicogenomics is a promising new tool for prediction of chemical toxicities including carcinogenicity in a relatively short period. However, it is important to develop a reliable animal test protocol for toxicogenomics studies. The preparation of RNA and tissues is also crucial, since it greatly influences outcomes of gene expression analysis. We proposed an animal test protocol for toxicogenomics studies. In the present study, we examined an animal test protocol by comparing biological and gene expression data from different laboratories running identical in vivo studies on the same microarray platform. The results gave good correspondence in all three laboratories at the level of biological responses and gene expression, especially for genes whose expression changes were quite large. As the fold change or the signal values become smaller, however, discrepancies occur in gene expression data. For example, one laboratory shows an opposite directional change to the other two or no change. The results of hierarchical clustering and principal component analysis (PCA) demonstrated all samples from the three laboratories being clearly divided between control and treatment. Examination of the reproducibility of gene expression data across laboratories using the proposed animal test protocol thus confirmed only minor differences, which was expected to present no problems for gene expression analysis.

  5. Studies with the USF/NASA toxicity screening test method - Exercise wheels and oxygen replenishment

    Science.gov (United States)

    Hilado, C. J.; Cumming, H. J.

    1977-01-01

    Continuing efforts to improve the University of San Francisco/NASA toxicity screening test method have included the addition of exercise wheels to provide a different measure of incapacitation, and oxygen replenishment to offset any effect of oxygen depletion by the test animals. The addition of exercise wheels limited the number of animals in each test and doubled the required number of tests without any significant improvement in reproducibility. Oxygen replenishment appears to have an effect on survival in the last 5 minutes of the 30-minute test, but the effect is expected to be similar for most materials.

  6. Animal experimentation in Japan: regulatory processes and application for microbiological studies.

    Science.gov (United States)

    Takahashi-Omoe, H; Omoe, K

    2007-07-01

    We have conducted animal experimentation as a highly effective technique in biological studies. Also in microbiological studies, we have used experimentation to prevent and treat many infectious diseases in humans and animals. In Japan, the 'Law for the Humane Treatment and Management of Animals', which covers the consideration of the three R principles, refinement, replacement and reduction for an international humane approach to animal experimentation came into effect in June 2006. Looking towards the straightforward operation of the law in animal experimentation, three government ministries established new basic guidelines for experimentation performed in their jurisdictional research and testing facilities. For future microbiological studies involving animals in Japan, we need to perform animal experiments according to the basic guidelines in association with overseas management systems. In this report, we discussed essential actions for the management of animal experimentation in microbiological studies in Japan.

  7. Why animal studies are still being used in drug development. An innovation system perspective

    NARCIS (Netherlands)

    Kooijman, M.

    2013-01-01

    In Europe alone, 3.6 million animals per year are used for drug development. Animal studies are worldwide the gold standard to evaluate the safety, efficacy and quality of drugs before these drugs are tested in humans. Nevertheless the value of animal studies to predict risks for humans has never be

  8. Animal models for studying dengue pathogenesis and therapy.

    Science.gov (United States)

    Chan, Kitti Wing Ki; Watanabe, Satoru; Kavishna, Ranmali; Alonso, Sylvie; Vasudevan, Subhash G

    2015-11-01

    Development of a suitable animal model for dengue virus disease is critical for understanding pathogenesis and for preclinical testing of antiviral drugs and vaccines. Many laboratory animal models of dengue virus infection have been investigated, but the challenges of recapitulating the complete disease still remain. In this review, we provide a comprehensive coverage of existing models, from man to mouse, with a specific focus on recent advances in mouse models for addressing the mechanistic aspects of severe dengue in humans. This article forms part of a symposium in Antiviral Research on flavivirus drug discovery.

  9. [Alcohol, tobacco and cannabis: Review of teratogenicity studies in animals].

    Science.gov (United States)

    Spézia, F

    2006-10-01

    Despite an intensive national campaign of information, the drugs most frequently consumed by young adults undoubtedly continue to be alcohol, tobacco and cannabis. If the impact of these drugs on the health of the consumers can be evaluated in conjunction with the clinical and epidemiologic data, the consequences on the embryo due to their consumption by the pregnant women can be appreciated thanks to the abundant literature describing their effects in the gravid animal. Taking into account the abundant literature available in multiple animal species, the zero drug recommendation should be widely diffused to pregnant women.

  10. Strategic focus on 3R principles reveals major reductions in the use of animals in pharmaceutical toxicity testing

    National Research Council Canada - National Science Library

    Törnqvist, Elin; Annas, Anita; Granath, Britta; Jalkesten, Elisabeth; Cotgreave, Ian; Öberg, Mattias

    2014-01-01

    ... numbers used in regulatory and investigatory in vivo studies. The work also details major factors influencing these reductions including the conception of ideas, cross-departmental working and acceptance into the work process...

  11. Miniaturized blood sampling techniques to benefit reduction in mice and refinement in nonhuman primates: applications to bioanalysis in toxicity studies with antibody-drug conjugates.

    Science.gov (United States)

    Caron, Alexis; Lelong, Christine; Pascual, Marie-Hélène; Benning, Véronique

    2015-03-01

    Minimizing the number of animals in regulatory toxicity studies while achieving study objectives to support the development of future medicines contributes to good scientific and ethical practices. Recent advances in technology have enabled the development of miniaturized blood sampling methods (including microsampling and dried blood spots) applicable to toxicokinetic determinations of small-molecule drugs. Implementation of miniaturized blood sampling methods in the context of biotherapeutic drugs is desirable because a limitation to this type of medicine remains the total blood volume needed from a single animal to support toxicokinetic determinations of several analytes (parent drug, metabolites[s], antidrug antibodies, and so forth). We describe here the technical details, applicability, and relevance of new miniaturized blood sampling procedures in mice and nonhuman primates in the context of the toxicologic evaluation of biotherapeutic drugs consisting of antibody-drug conjugates developed for oncology indications. These examples illustrate how these techniques can benefit the reduction of animal usage in mouse toxicity studies by decreasing the number of animals dedicated to toxicokinetic determinations and the refinement of practices in nonhuman primate toxicity studies by decreasing the blood volume repeatedly drawn for toxicokinetic determinations.

  12. Miniaturized Blood Sampling Techniques to Benefit Reduction in Mice and Refinement in Nonhuman Primates: Applications to Bioanalysis in Toxicity Studies with Antibody–Drug Conjugates

    Science.gov (United States)

    Caron, Alexis; Lelong, Christine; Pascual, Marie-Hélène; Benning, Véronique

    2015-01-01

    Minimizing the number of animals in regulatory toxicity studies while achieving study objectives to support the development of future medicines contributes to good scientific and ethical practices. Recent advances in technology have enabled the development of miniaturized blood sampling methods (including microsampling and dried blood spots) applicable to toxicokinetic determinations of small-molecule drugs. Implementation of miniaturized blood sampling methods in the context of biotherapeutic drugs is desirable because a limitation to this type of medicine remains the total blood volume needed from a single animal to support toxicokinetic determinations of several analytes (parent drug, metabolites[s], antidrug antibodies, and so forth). We describe here the technical details, applicability, and relevance of new miniaturized blood sampling procedures in mice and nonhuman primates in the context of the toxicologic evaluation of biotherapeutic drugs consisting of antibody–drug conjugates developed for oncology indications. These examples illustrate how these techniques can benefit the reduction of animal usage in mouse toxicity studies by decreasing the number of animals dedicated to toxicokinetic determinations and the refinement of practices in nonhuman primate toxicity studies by decreasing the blood volume repeatedly drawn for toxicokinetic determinations. PMID:25836960

  13. Studies on the prenatal toxicity of toluene in rabbits following inhalation exposure and proposal of a pregnancy guidance value

    Energy Technology Data Exchange (ETDEWEB)

    Klimisch, H.J.; Hellwig, J. (BASF AG, Ludwigshafen am Rhein (Germany). Abt. fuer Toxikologie); Hofmann, A. (Merck (E.), Darmstadt (Germany). Inst. fuer Toxikologie)

    1992-07-01

    Prenatal toxicity of toluene was determined in two separate studies by inhalation exposure of Himalayan rabbits. In the first study 15 artificially inseminated females per group were exposed to 30, 100, or 300 ppm and in the second study 20 artificially inseminated females per group inhaled 100 or 500 ppm. In each case the rabbits were exposed for 6 hours per day from day 6 post-insemination (p.i.) to day 18 p.i. The respective controls inhaled conditioned clean air under the same exposure conditions. No signs of maternal toxicity were observed. All data obtained on gestational parameters were found to be within the variation range reported for this rabbit strain. The fetal external, soft tissue and skeletal findings, were seen in toluene exposed fetuses in a frequency similar to the corresponding and/or historical controls. Differences observed between the groups were not concentration dependent and were considered incidental rather than compound related. Therefore, toluene was not embryotoxic, fetotoxic, or teratogenic for rabbits exposed during the period of organogenesis. The highest concentration tested under these conditions (500 ppm) was found to be a no-observable-adverse-effect level (NOAEL) for both the adult and the fetal Himalayan rabbit. Based on these and previous results of animal studies of prenatal toxicity, a safety or uncertainty factor approach is considered for setting limits of exposure for women at workplaces. A pregnancy guidance value of 20 ppm is proposed. (orig.).

  14. A 90-day oral (dietary) toxicity study of rebaudioside A in Sprague-Dawley rats.

    Science.gov (United States)

    Nikiforov, Andrey I; Eapen, Alex K

    2008-01-01

    Rebaudioside A is one of several glycosides found in the leaves of Stevia rebaudiana (Bertoni) Bertoni (Compositae) stevia that has been identified as a potential sweetener. The present study (initiated in April 2006 and completed in October 2006) evaluated the safety of this sweetener when administered as a dietary admix at target exposure levels of 500, 1000, and 2000 mg/kg/day to Sprague-Dawley rats for 90 days. There were no treatment-related effects on the general condition and behavior of the animals as determined by clinical observations, functional observational battery, and locomotor activity assessments. Evaluation of clinical pathology parameters revealed no toxicologically relevant, treatment-related effects on hematology, serum chemistry, or urinalysis. Macroscopic and microscopic findings revealed no treatment-related effects on any organ evaluated. Lower mean body weight gains were noted in males in the 2000 mg/kg/day group throughout the study, which was considered to be test article related; however, given the small magnitude of the difference as compared to controls, this effect was not considered to be adverse. Results of this study clearly demonstrate that dietary administration of high concentrations of rebaudioside A for 90 consecutive days to Sprague-Dawley rats was not associated with any signs of toxicity.

  15. Acute Oral Toxicity Studies of Ethanol Leaf Extracts Of Derris Scandens & Pulicaria Wightiana In Albino Rats

    Directory of Open Access Journals (Sweden)

    Vidya Sabbani

    2015-02-01

    Full Text Available Objective: The present study was designed to find out LD50 and to ascertain the safety of ethanol extracts of leaves of Derris scan dens and Pulicaria wightiana by acute oral toxicity study in female rats as per OECD guideline 425.Methods: Rats were sequentially administered with ethanol leaf extracts of Derris scandens (Ds & Pulicaria wightiana(Pw  in single dosages of 175, 550, and 2000 mg/kg of body weight. All the animals were individually studied for mortality, wellness parameters and body weight for 14 days.Results: No mortality and no significant changes were observed in body weight and wellness parameters at 175, 550 and 2000 mg/kg body wt. doses of both Derris scandens and Pulicaria wightiana , which reveal the safety of these plants  in the doses up to 2000 mg/kg body weight.Conclusion: Conclusively, LD50 value of ethanol extracts of leaves of Derris scandens and Pulicaria wightiana were found to be more than 2000 mg/kg body weight.

  16. Sub-acute toxicity studies of acetaminophen in Sprague Dawley rats.

    Science.gov (United States)

    Venkatesan, Pachaiyappan Sampath; Deecaraman, Munuswamy; Vijayalakshmi, Melanathuru; Sakthivelan, Sigamany Masilamani

    2014-01-01

    The aim of the present study was to evaluate the sub-acute oral toxicity of acetaminophen in Sprague Dawley (SD) rats at 250 to 1000 mg/kg body weight (b.wt.). The following observations were noticed during the study. No mortality in male and female rats, at and up to the dose of 1000 mg/kg b.wt. There were abnormal clinical signs observed on female animals at 1000 mg/kg b.wt. dose level. There were no difference in body weight gain and no effect on the daily feed consumption. No toxicologically significant effect on the haematological parameters but liver and kidney related biochemical parameter showed significant difference at 1000 mg/kg b.wt. in females. No toxicologically significant effect on the urinalysis parameters, absolute and relative organ weights and gross pathological alterations; whereas histopathological alterations were observed in female liver at dose level of 1000 mg/kg b.wt. were observed. Based on the findings of this study, the No Observed Adverse Effect Level (NOAEL) of acetaminophen in SD rats, following oral administration at the doses of 250, 500 and 1000 mg/kg on daily basis was found to be 500 mg/kg b.wt.

  17. Genotoxicity and subchronic toxicity studies of DHA-rich oil in rats.

    Science.gov (United States)

    Blum, René; Kiy, Thomas; Tanaka, Satohiro; Wong, Andrea W; Roberts, Ashley

    2007-12-01

    Polyunsaturated fatty acids, including docosahexaenoic acid (DHA), are natural constituents of the human diet. DHA-algal oil is produced through the use of the non-toxigenic and non-pathogenic marine protist, Ulkenia sp. The safety of DHA-algal oil was assessed in a subchronic toxicity study and in genotoxicity studies. In a 90-day study, rats were orally administered water or DHA-algal oil at concentrations of 0, 500, 1000, and 2000 mg/kg in combination with 2000, 1500, 1000 or 0 mg/kg DHA-containing fish oil, respectively. Additional animals were administered water, 2000 mg/kg DHA-algal oil, or 2000 mg/kg fish oil for 90 days, followed by a 4-week recovery phase. No treatment-related effects were observed in clinical observations, food and water consumption, mortality, gross pathology, and histopathology. Increased body weights and liver weights in oil-treated groups were attributed to the large lipid load and were not regarded as toxicologically significant. Furthermore, no treatment-related differences in the measured parameters between the DHA-algal oil and fish oil groups were detected. In genotoxicity experiments, DHA-algal oil exerted no mutagenic activity in various bacterial strains, nor did it induce chromosomal aberrations in Chinese hamster fibroblast cells. These results support the safety of DHA-algal oil as a dietary source of DHA.

  18. Subchronic oral toxicity studies with erythritol in mice and rats

    NARCIS (Netherlands)

    Til, H.P.; Kuper, C.F.; Falke, H.E.; Bär, A.

    1996-01-01

    Erythritol is a sugar alcohol (polyol) with potential applications as a low-calorie, bulk sweetener. Ingested erythritol is efficiently absorbed and excreted unchanged via the urine since it is not metabolized systemically by the animal or human body. Erythritol was administered to four groups of 10

  19. Subchronic oral toxicity studies with erythritol in mice and rats

    NARCIS (Netherlands)

    Til, H.P.; Kuper, C.F.; Falke, H.E.; Bär, A.

    1996-01-01

    Erythritol is a sugar alcohol (polyol) with potential applications as a low-calorie, bulk sweetener. Ingested erythritol is efficiently absorbed and excreted unchanged via the urine since it is not metabolized systemically by the animal or human body. Erythritol was administered to four groups of 10

  20. hepatorenal toxicity studies of sub-chronic administration of calyx ...

    African Journals Online (AJOL)

    DR. AMINU

    A decreased in weights of the animals were observed at all dose levels. ... and direct bilirubin increased significantly (p<0.05) in comparison to the control. ... The plant finds various .... within the cells of the liver, heart, kidney, gill, muscle.

  1. Markerless 3D motion capture for animal locomotion studies

    Directory of Open Access Journals (Sweden)

    William Irvin Sellers

    2014-06-01

    Full Text Available Obtaining quantitative data describing the movements of animals is an essential step in understanding their locomotor biology. Outside the laboratory, measuring animal locomotion often relies on video-based approaches and analysis is hampered because of difficulties in calibration and often the limited availability of possible camera positions. It is also usually restricted to two dimensions, which is often an undesirable over-simplification given the essentially three-dimensional nature of many locomotor performances. In this paper we demonstrate a fully three-dimensional approach based on 3D photogrammetric reconstruction using multiple, synchronised video cameras. This approach allows full calibration based on the separation of the individual cameras and will work fully automatically with completely unmarked and undisturbed animals. As such it has the potential to revolutionise work carried out on free-ranging animals in sanctuaries and zoological gardens where ad hoc approaches are essential and access within enclosures often severely restricted. The paper demonstrates the effectiveness of video-based 3D photogrammetry with examples from primates and birds, as well as discussing the current limitations of this technique and illustrating the accuracies that can be obtained. All the software required is open source so this can be a very cost effective approach and provides a methodology of obtaining data in situations where other approaches would be completely ineffective.

  2. Toxicity study of reclaimed water on human embryonic kidney cells.

    Science.gov (United States)

    Ren, Xianghao; Kou, Ying-Ying; Kim, Taeeung; Chae, Kyu-Jung; Ng, How Yong

    2017-08-28

    The importance of evaluating the toxic effects associated with the use of reclaimed water has been increasing. The purpose of this research was to investigate the cytotoxicity and molecular toxicity of reclaimed water on the human embryonic kidney 293 (HEK293) cells. The culture medium was synthesized using the reclaimed water samples. Wastewater treatment plant influent (WTI) and effluent (WTE), containing micropollutants at the nanogram per liter level, decreased cell proliferation (93.4-98.9% and 91.5-96.6% of the control, respectively) and increased cell damage (103.6-117.5% and 100.7-109% of the control, respectively) at all exposure times, except for a decrease in cell damage observed after an 8-h exposure to WTE. Membrane bioreactor permeate (MBRP) increased cell proliferation (102.1-106.7% of the control) and decreased cell damage at 8 and 12 h (92.4 and 98.4% of the control, respectively), but slightly increased cell damage at 24 h and later time points (101.1-104.9% of the control). All three water samples induced cell apoptosis (120.9-123.4% of the control). They also affected the expression of cell-cycle regulatory proteins (p16(INK4a), p27(Kip1), cyclin-dependent kinases 2 and 4, cyclin D1, and cyclin E) and apoptosis-related regulatory proteins (p-JNK, Bcl-2, caspase-9, and caspase-3). In conclusion, all three water samples showed cytotoxicity and molecular toxicity in the HEK293 cells, and the results of the cell-cycle and apoptosis regulatory protein expression after WTI and WTE treatments were consistent with the results of the cytotoxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. A Structural Modelling Study on Marine Sediments Toxicity

    Directory of Open Access Journals (Sweden)

    Sorana D. Bolboacă

    2008-06-01

    Full Text Available Quantitative structure-activity relationship models were obtained by applying the Molecular Descriptor Family approach to eight ordnance compounds with different toxicity on five marine species (arbacia punctulata, dinophilus gyrociliatus, sciaenops ocellatus, opossum shrimp, and ulva fasciata. The selection of the best among molecular descriptors generated and calculated from the ordnance compounds structures lead to accurate monovariate models. The resulting models obtained for six endpoints proved to be accurate in estimation (the squared correlation coefficient varied from 0.8186 to 0.9997 and prediction (the correlation coefficient obtained in leave-one-out analysis varied from 0.7263 to 0.9984.

  4. Simple models for studying complex spatiotemporal patterns of animal behavior

    Science.gov (United States)

    Tyutyunov, Yuri V.; Titova, Lyudmila I.

    2017-06-01

    Minimal mathematical models able to explain complex patterns of animal behavior are essential parts of simulation systems describing large-scale spatiotemporal dynamics of trophic communities, particularly those with wide-ranging species, such as occur in pelagic environments. We present results obtained with three different modelling approaches: (i) an individual-based model of animal spatial behavior; (ii) a continuous taxis-diffusion-reaction system of partial-difference equations; (iii) a 'hybrid' approach combining the individual-based algorithm of organism movements with explicit description of decay and diffusion of the movement stimuli. Though the models are based on extremely simple rules, they all allow description of spatial movements of animals in a predator-prey system within a closed habitat, reproducing some typical patterns of the pursuit-evasion behavior observed in natural populations. In all three models, at each spatial position the animal movements are determined by local conditions only, so the pattern of collective behavior emerges due to self-organization. The movement velocities of animals are proportional to the density gradients of specific cues emitted by individuals of the antagonistic species (pheromones, exometabolites or mechanical waves of the media, e.g., sound). These cues play a role of taxis stimuli: prey attract predators, while predators repel prey. Depending on the nature and the properties of the movement stimulus we propose using either a simplified individual-based model, a continuous taxis pursuit-evasion system, or a little more detailed 'hybrid' approach that combines simulation of the individual movements with the continuous model describing diffusion and decay of the stimuli in an explicit way. These can be used to improve movement models for many species, including large marine predators.

  5. Inhalation toxicity and carcinogenicity studies of cobalt sulfate.

    Science.gov (United States)

    Bucher, J R; Hailey, J R; Roycroft, J R; Haseman, J K; Sills, R C; Grumbein, S L; Mellick, P W; Chou, B J

    1999-05-01

    Cobalt sulfate is a water-soluble cobalt salt with a variety of industrial and agricultural uses. Several cobalt compounds have induced sarcomas at injection sites in animals, and reports have suggested that exposure to cobalt-containing materials may cause lung cancer in humans. The present studies were done because no adequate rodent carcinogenicity studies had been performed with a soluble cobalt salt using a route relevant to occupational exposures. Groups of 50 male and 50 female F344/N rats and B6C3F1 mice were exposed to aerosols containing 0, 0.3, 1.0, or 3.0 mg/m3 cobalt sulfate hexahydrate, 6 h/day, 5 days/week, for 104 weeks. Survival and body weights of exposed rats and mice were generally unaffected by the exposures. In rats, proteinosis, alveolar epithelial metaplasia, granulomatous alveolar inflammation, and interstitial fibrosis were observed in the lung in all exposed groups. Nonneoplastic lesions of the nose and larynx were also attributed to exposure to all concentrations of cobalt sulfate. In 3.0 mg/m3 male rats and in female rats exposed to 1.0 or 3.0 mg/m3, the incidences of alveolar/bronchiolar neoplasms were increased over those in the control groups. Lung tumors occurred with significant positive trends in both sexes. The incidences of adrenal pheochromocytoma in 1.0 mg/m3 male rats and in 3.0 mg/m3 female rats were increased. Nonneoplastic lesions of the respiratory tract were less severe in mice than in rats. In mice, alveolar/bronchiolar neoplasms in 3.0 mg/m3 males and females were greater than those in the controls, and lung tumors occurred with significantly positive trends. Male mice had liver lesions consistent with a Helicobacter hepaticus infection. Incidences of liver hemangiosarcomas were increased in exposed groups of male mice; however, because of the infection, no conclusion could be reached concerning an association between liver hemangiosarcomas and cobalt sulfate. In summary, exposure to cobalt sulfate by inhalation

  6. Study of crotoxin on the induction of paralysis in extraocular muscle in animal model

    Directory of Open Access Journals (Sweden)

    Geraldo de Barros Ribeiro

    2012-10-01

    Full Text Available PURPOSE: Crotoxin is the major toxin of the venom of the South American rattlesnake Crotalus durissus terrificus, capable of causing a blockade of the neurotransmitters at the neuromuscular junction. The objective of this study was to appraise the action and effectiveness of the crotoxin induced paralysis of the extraocular muscle and to compare its effects with the botulinum toxin type A (BT-A. METHODS: The crotoxin, with LD50 of 1.5 µg, was injected into the superior rectus muscle in ten New Zealand rabbits. The concentration variance was 0.015 up to 150 µg. Two rabbits received 2 units of botulinum toxin type A for comparative analysis. The evaluation of the paralysis was performed using serial electromyography. After the functional recovery of the muscles, which occurred after two months, six rabbits were sacrificed for anatomopathology study. RESULTS: The animals did not show any evidence of systemic toxicity. Transitory ptosis was observed in almost every animal and remained up to fourteen days. These toxins caused immediate blockade of the electrical potentials. The recovery was gradual in the average of one month with regeneration signs evident on the electromyography. The paralysis effect of the crotoxin on the muscle was proportional to its concentration. The changes with 1.5 µg crotoxin were similar to those produced by the botulinum toxin type A. The histopathology findings were localized to the site of the injection. No signs of muscle fiber's necrosis were seen in any sample. The alterations induced by crotoxin were also proportional to the concentration and similar to botulinum toxin type A in concentration of 1.5 µg. CONCLUSION: Crotoxin was able to induce transitory paralysis of the superior rectus muscle. This effect was characterized by reduction of action potentials and non-specific signs of fibrillation. Crotoxin, in concentration of 1.5 µg was able to induce similar effects as botulinum toxin type A.

  7. Meta-Analyses of Animal Studies: An Introduction of a Valuable Instrument to Further Improve Healthcare

    Science.gov (United States)

    Hooijmans, Carlijn R.; IntHout, Joanna; Ritskes-Hoitinga, Merel; Rovers, Maroeska M.

    2014-01-01

    In research aimed at improving human health care, animal studies still play a crucial role, despite political and scientific efforts to reduce preclinical experimentation in laboratory animals. In animal studies, the results and their interpretation are not always straightforward, as no single study is executed perfectly in all steps. There are several possible sources of bias, and many animal studies are replicates of studies conducted previously. Use of meta-analysis to combine the results of studies may lead to more reliable conclusions and a reduction of unnecessary duplication of animal studies. In addition, due to the more exploratory nature of animal studies as compared to clinical trials, meta-analyses of animal studies have greater potential in exploring possible sources of heterogeneity. There is an abundance of literature on how to perform meta-analyses on clinical data. Animal studies, however, differ from clinical studies in some aspects, such as the diversity of animal species studied, experimental design, and study characteristics. In this paper, we will discuss the main principles and practices for meta-analyses of experimental animal studies. PMID:25541544

  8. Acute toxicity and hepatotoxicokinetic studies of Tamarindus indica extract.

    Science.gov (United States)

    Nwodo, Uchechukwu U; Ngene, Augustine A; Anaga, Aruh O; Chigor, Vincent N; Henrietta, Igbinosa I; Okoh, Anthony I

    2011-08-31

    Tamarindus indica is widely used as a food and beverage and in traditional medicine. The apparent lack of dose standardization in herbal medicine necessitates the evaluation of the lethality T. indica on Artemia salina nauplii and chicken embryos via in vitro and in vivo techniques. Furthermore, hepatotoxicokinetics of the crude extract and fractions on Wister rats was also assessed. At concentrations of 200, 20 and 2 µg/mL, crude extract and fractions showed brine shrimp death percentages ranging from 86.70% to 3.30% and the sub-fractions showed death percentage ranges of 46.70% to 3.30%. Calculated LD₅₀ values ranged from 832 µg/mL to 5,019 µg/mL. Dosing Wister rats with 25% and 50% concentration of LD₅₀ determined for crude extract and fractions on chicken embryos showed an elevation in the ALT and AST levels in the serum. Brine shrimps and chicken embryos showed a positive correlation, with R² values of 0.541 and 0.588 (P ≤ 0.05) for fractions and subfractions, respectively, as media for the lethality assay. Dose standardization in folk herbal medicine is imperative as T. indica used as food and medicine has been shown to be toxic at high doses. Brine shrimp and chicken embryos may be comparably used as medium for toxicity assay.

  9. Safety Evaluation of Oral Toxicity of Carica papaya Linn. Leaves: A Subchronic Toxicity Study in Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Zakiah Ismail

    2014-01-01

    Full Text Available The subchronic toxicity effect of the leaf extract of Carica papaya Linn. in Sprague Dawley (SD rats was investigated in this study. The extract was prepared by dissolving the freeze dried extract of the leaves in distilled water and was administered orally to SD rats (consisted of 10 rats/sex/group at 0 (control, 0.01, 0.14, and 2 g/kg body weight (BW for 13 weeks. General observation, mortality, and food and water intake were monitored throughout the experimental period. Hematological and biochemical parameters, relative organ weights, and histopathological changes were evaluated. The study showed that leaf extract when administered for 13 weeks did not cause any mortality and abnormalities of behavior or changes in body weight as well as food and water intake. There were no significant differences observed in hematology parameters between treatment and control groups; however significant differences were seen in biochemistry values, for example, LDH, creatinine, total protein, and albumin. However, these changes were not associated with histopathological changes. In conclusion, the results suggested that daily oral administration of rats with C. papaya leaf extract for 13 weeks at a dose up to fourteen times the levels employed in traditional medicine practice did not cause any significant toxic effect.

  10. [Selective toxicity of cytostatic agents: studies on the cardiotoxicity of doxorubicin, its pathogenesis and contraindications].

    Science.gov (United States)

    Lenzhofer, R

    1983-01-01

    In the past few years the medical treatment of malignant diseases has steadily increased in scope and importance. However, the tumor regimens described in the textbooks still are rather schematic recommendations, which are inadequately tailored to the needs of the individual case. Current tumor therapy is based on the results of the statistical analysis using empirical data collected in randomized trials. While patients can today be given a statistical value which expresses their computed chance of a cure versus that of a defined population, there is still no generally valid method which could serve as a rational basis for individualized counselling. But cytostatic chemotherapy has yet another major shortcoming: the collective assessment of toxicity, which is related to one of the basic properties of cytostatic drugs, i.e. their extremely low therapeutic index. Many of the side effects of cytostatics may cause severe irreversible, at times even fatal, organ dysfunction. Consequently, the definition of the therapeutic risks involved on the basis of an objective identification of potential organ toxicity is a major challenge. "Surgery without a knife", as K.H. Spitzy has called chemotherapy, should be subjected to objective criteria for its indications and contraindications so that patients can truly benefit from what are become increasingly aggressive measures. The principle of weighing the benefits desired in the individual case against the potential risks involved in a specific treatment, which Paul Ehrlich postulated for antibacterial chemotherapy, should also be applied to cytostatic chemotherapy with a view to facilitating the decision for or against therapy in borderline cases. The present contribution which is designed to shed light on the cardiotoxicity of doxorubicin should be interpreted in light of this situation. Pathogenetic aspects and animal experiments on drug-induced lipid peroxidation will be discussed and clinical trials on both acute and chronic

  11. Alpha -tocopherol supplementation on chromium toxicity : a study on rat liver and kidney cell membrane

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Membrane damage is one of the important consequence of chromium, an environmental toxicant, to produce cytotoxicity. α-tocopherol, a membrane protectant can be used to reduce the chromium-induced membrane damage. In the present study, the impact of chromium in presence and absence of α-tocopherol was studied on plasma membrane of liver and kidney in male Wistar rats (80 - 100g body weight). Significant increase in membrane cholesterol level as well as significant decrease in membrane phospholipid level in chromium exposed ( 0.8 mg /100g body weight/d, i.p., for 4 weeks) animals suggest structural alteration of both liver and kidney plasma memebrane. The alkaline phosphatase, total ATPase and Na+-K+-ATPase activities of plasma membrane were significantly decreased in both liver and kidney after chromium treatment. However, α-tocopherol (30 mg / 100g diet) supplementation can restrict the changes in these membrane-bound enzyme activities. Thus, the usefulness of dietary supplementation of α-tocopherol to restrain the chromium-induced membrane damage is suggested.

  12. 90-Day subchronic toxicity study of sodium molybdate dihydrate in rats.

    Science.gov (United States)

    Murray, F Jay; Sullivan, Frank M; Tiwary, Asheesh K; Carey, Sandra

    2014-12-01

    This study investigated the subchronic toxicity of molybdenum (Mo) in Sprague-Dawley rats given sodium molybdate dihydrate in the diet for 90days at dose levels of 0, 5, 17 or 60mgMo/kgbw/day. The study complied with OECD Test Guideline (TG) 408, with additional examination of estrus cycles and sperm count, motility, and morphology from OECD TG 416. The overall no-observed-adverse-effect level was 17mgMo/kgbw/day, based on effects on body weight, body weight gain, food conversion efficiency and renal histopathology (females only) at 60mgMo/kgbw/day. No treatment-related adverse effects on reproductive organ weights or histopathology, estrus cycles or sperm parameters were observed at any dose level. No adverse effects were observed in the high dose animals after the 60-day recovery period, with the exception that male rats did not fully recover from reduced body weight. Serum blood, liver and kidney samples were analyzed for molybdenum, copper, zinc, manganese, iron, cobalt and selenium; high levels of molybdenum and copper were found in the serum, blood, liver and kidneys of rats treated with 60mgMo/kgbw/day. In conclusion, the LOAEL and NOAEL for molybdenum were determined to be 60 and 17mgMo/kgbw/day, respectively.

  13. A one-generation reproductive toxicity study of ethyl tertiary butyl ether in rats.

    Science.gov (United States)

    Fujii, Sakiko; Yabe, Kaoru; Furukawa, Masatoshi; Matsuura, Masao; Aoyama, Hiroaki

    2010-11-01

    A one-generation reproductive toxicity study was conducted to evaluate the effects of ethyl tertiary butyl ether (ETBE), a bio-fuel, on reproduction of parental rats, as well as development and growth of their offspring at dose levels of 0, 100, 300 and 1000 mg/kg-d by gavage. No treatment-related changes were observed in either F0 parents or their F1 offspring in the 100 and 300 mg/kg groups in any parameters examined. Some parental animals in the 1000 mg/kg group exhibited transient salivation, possibly a reflex to a bitter taste of ETBE, immediately after dosing, although their body weights, food consumption, reproductive parameters, and gross pathological findings were not affected. Their absolute and relative liver weights increased significantly in the 1000 mg/kg group, suggesting enhanced activities of metabolic enzymes. Pup viability was slightly reduced during the early lactation period in the 1000 mg/kg group. These results lead to the conclusion that the no-observed-adverse-effect-level (NOAEL) of ETBE on both parental rats and their offspring is 300 mg/kg-d under the current study condition.

  14. Towards Global QSAR Model Building for Acute Toxicity: Munro Database Case Study

    Directory of Open Access Journals (Sweden)

    Swapnil Chavan

    2014-10-01

    Full Text Available A series of 436 Munro database chemicals were studied with respect to their corresponding experimental LD50 values to investigate the possibility of establishing a global QSAR model for acute toxicity. Dragon molecular descriptors were used for the QSAR model development and genetic algorithms were used to select descriptors better correlated with toxicity data. Toxic values were discretized in a qualitative class on the basis of the Globally Harmonized Scheme: the 436 chemicals were divided into 3 classes based on their experimental LD50 values: highly toxic, intermediate toxic and low to non-toxic. The k-nearest neighbor (k-NN classification method was calibrated on 25 molecular descriptors and gave a non-error rate (NER equal to 0.66 and 0.57 for internal and external prediction sets, respectively. Even if the classification performances are not optimal, the subsequent analysis of the selected descriptors and their relationship with toxicity levels constitute a step towards the development of a global QSAR model for acute toxicity.

  15. The ability of animal studies to detect serious post marketing adverse events is limited.

    Science.gov (United States)

    van Meer, Peter J K; Kooijman, Marlous; Gispen-de Wied, Christine C; Moors, Ellen H M; Schellekens, Huub

    2012-12-01

    The value of animal studies to assess drug safety is unclear because many such studies are biased and have methodological shortcomings. We studied whether post-marketing serious adverse reactions to small molecule drugs could have been detected on the basis of animal study data included in drug registration files. Of 93 serious adverse reactions related to 43 small molecule drugs, only 19% were identified in animal studies as a true positive outcome, which suggests that data from animal studies are of limited value to pharmacovigilance activities. Our study shows that drug registration files can be used to study the predictive value of animal studies and that the value of animal studies in all stages of the drug development should be investigated in a collaborative endeavour between regulatory authorities, industry, and academia. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. The usefulness of systematic reviews of animal experiments for the design of preclinical and clinical studies

    NARCIS (Netherlands)

    Vries, R.B.M. de; Wever, K.E.; Avey, M.T.; Stephens, M.L.; Sena, E.S.; Leenaars, M.

    2014-01-01

    The question of how animal studies should be designed, conducted, and analyzed remains underexposed in societal debates on animal experimentation. This is not only a scientific but also a moral question. After all, if animal experiments are not appropriately designed, conducted, and analyzed, the

  17. A search filter for increasing the retrieval of animal studies in Embase

    NARCIS (Netherlands)

    Vries, R.B.M. de; Hooijmans, C.R.; Tillema, A.; Leenaars, M.; Ritskes-Hoitinga, M.

    2011-01-01

    Collecting and analysing all available literature before starting a new animal experiment is important and it is indispensable when writing systematic reviews of animal research. In practice, finding all animal studies relevant to a specific research question turns out to be anything but simple. In

  18. Collaborative work on evaluation of ovarian toxicity. 2) Two- or four-week repeated dose studies and fertility study of mifepristone in female rats.

    Science.gov (United States)

    Tamura, Toru; Yokoi, Ryohei; Okuhara, Yuji; Harada, Chiho; Terashima, Yukari; Hayashi, Morimichi; Nagasawa, Tatsuya; Onozato, Tomoya; Kobayashi, Kazuo; Kuroda, Junji; Kusama, Hiroshi

    2009-01-01

    In order to assess ovarian pathological changes and their relationship to changes in female fertility parameters, mifepristone, a progesterone receptor antagonist, was selected as the test article and was administered orally to female rats at dose levels of 0, 0.8, 4, 20 and 100 mg/kg for 2 or 4 weeks in repeated dose-toxicity studies and in a female fertility study at dose levels of 0, 0.8, 4 and 20 mg/kg from > 2 weeks before copulation to postcoital day 7. In the repeated dose toxicity studies, persistent estrus was seen in the vaginal smears, and multiple cysts in the ovaries at necropsy, increases in luteinized cysts and hypertrophy of previously formed corpora lutea were observed in the histopathological examination of ovaries in rats receiving 20 mg/kg or more for 2 or 4 weeks. In female fertility studies, persistent vaginal cornification was also observed at 20 mg/kg and the precoital interval was significantly shortened. All of the animals were completely infertile when dosed with 20 mg/kg during the post-coital period. An increase in pre-implantation losses was observed in the animals treated with 20 mg/kg during the pre-coital phase, while treatment with 4 mg/kg mifepristone during the post-coital phase induced an increase in post-implantation losses. These results suggested that a 2-week administration period would be sufficient to detect the ovarian toxicity of mifepristone in repeated dose toxicity study and the pathological findings in the ovaries would reflect the alterations in female reproductive endpoints in the female fertility study.

  19. Preclinical rodent toxicity studies for long term use of ceftriaxone

    Directory of Open Access Journals (Sweden)

    Elena Ratti

    2015-01-01

    Ceftriaxone showed rapid absorption with half-life values ranging between 1 and 1.5 h. Additionally, there was no evidence of accumulation and a virtually complete elimination by 16 h after the last dose. Overall there were no toxicologically meaningful drug-related animal findings associated with the long-term administration (6 months of ceftriaxone. These results support safety of long-term use of ceftriaxone in human clinical trials.

  20. Six-month low level chlorine dioxide gas inhalation toxicity study with two-week recovery period in rats

    Science.gov (United States)

    2012-01-01

    Background Chlorine dioxide (CD) gas has a potent antimicrobial activity at extremely low concentration and may serve as a new tool for infection control occupationally as well as publicly. However, it remains unknown whether the chronic exposure of CD gas concentration effective against microbes is safe. Therefore, long-term, low concentration CD gas inhalation toxicity was studied in rats as a six-month continuous whole-body exposure followed by a two-week recovery period, so as to prove that the CD gas exposed up to 0.1 ppm (volume ratio) is judged as safe on the basis of a battery of toxicological examinations. Methods CD gas at 0.05 ppm or 0.1 ppm for 24 hours/day and 7 days/week was exposed to rats for 6 months under an unrestrained condition with free access to chow and water in a chamber so as to simulate the ordinary lifestyle in human. The control animals were exposed to air only. During the study period, the body weight as well as the food and water consumptions were recorded. After the 6-month exposure and the 2-week recovery period, animals were sacrificed and a battery of toxicological examinations, including biochemistry, hematology, necropsy, organ weights and histopathology, were performed. Results Well regulated levels of CD gas were exposed throughout the chamber over the entire study period. No CD gas-related toxicity sign was observed during the whole study period. No significant difference was observed in body weight gain, food and water consumptions, and relative organ weight. In biochemistry and hematology examinations, changes did not appear to be related to CD gas toxicity. In necropsy and histopathology, no CD gas-related toxicity was observed even in expected target respiratory organs. Conclusions CD gas up to 0.1 ppm, exceeding the level effective against microbes, exposed to whole body in rats continuously for six months was not toxic, under a condition simulating the conventional lifestyle in human. PMID:22348507

  1. Six-month low level chlorine dioxide gas inhalation toxicity study with two-week recovery period in rats

    Directory of Open Access Journals (Sweden)

    Akamatsu Akinori

    2012-02-01

    Full Text Available Abstract Background Chlorine dioxide (CD gas has a potent antimicrobial activity at extremely low concentration and may serve as a new tool for infection control occupationally as well as publicly. However, it remains unknown whether the chronic exposure of CD gas concentration effective against microbes is safe. Therefore, long-term, low concentration CD gas inhalation toxicity was studied in rats as a six-month continuous whole-body exposure followed by a two-week recovery period, so as to prove that the CD gas exposed up to 0.1 ppm (volume ratio is judged as safe on the basis of a battery of toxicological examinations. Methods CD gas at 0.05 ppm or 0.1 ppm for 24 hours/day and 7 days/week was exposed to rats for 6 months under an unrestrained condition with free access to chow and water in a chamber so as to simulate the ordinary lifestyle in human. The control animals were exposed to air only. During the study period, the body weight as well as the food and water consumptions were recorded. After the 6-month exposure and the 2-week recovery period, animals were sacrificed and a battery of toxicological examinations, including biochemistry, hematology, necropsy, organ weights and histopathology, were performed. Results Well regulated levels of CD gas were exposed throughout the chamber over the entire study period. No CD gas-related toxicity sign was observed during the whole study period. No significant difference was observed in body weight gain, food and water consumptions, and relative organ weight. In biochemistry and hematology examinations, changes did not appear to be related to CD gas toxicity. In necropsy and histopathology, no CD gas-related toxicity was observed even in expected target respiratory organs. Conclusions CD gas up to 0.1 ppm, exceeding the level effective against microbes, exposed to whole body in rats continuously for six months was not toxic, under a condition simulating the conventional lifestyle in human.

  2. Regulatory Forum opinion piece: New testing paradigms for reproductive and developmental toxicity--the NTP modified one generation study and OECD 443.

    Science.gov (United States)

    Foster, Paul M D

    2014-12-01

    The National Toxicology Program (NTP) has developed a new flexible study design, termed the modified one generation (MOG) reproduction study. The MOG study will encompass measurements of developmental and reproductive toxicity parameters as well as enable the setting of appropriate dose levels for a cancer bioassay through evaluation of target organ toxicity that is based on test article exposure that starts during gestation. This study design is compared and contrasted with the new Organization for Economic Co-operation and Development (OECD) 443 test guideline, the extended one generation reproduction study. The MOG study has a number of advantages, with a focus on F 1 animals, the generation of adequately powered, robust data sets that include both pre and postnatal developmental toxicity information, and the measurement of effects on reproductive structure and function in the same animals. This new study design does not employ the use of internal triggers in the design structure for the use of animals already on test and is also consistent with the principles of the 3R's. © 2014 by The Author(s).

  3. A global pharmaceutical company initiative: an evidence-based approach to define the upper limit of body weight loss in short term toxicity studies.

    Science.gov (United States)

    Chapman, Kathryn; Sewell, Fiona; Allais, Linda; Delongeas, Jean-Luc; Donald, Elizabeth; Festag, Matthias; Kervyn, Sophie; Ockert, Deborah; Nogues, Vicente; Palmer, Helen; Popovic, Marija; Roosen, Wendy; Schoenmakers, Ankie; Somers, Kevin; Stark, Claudia; Stei, Peter; Robinson, Sally

    2013-10-01

    Short term toxicity studies are conducted in animals to provide information on major adverse effects typically at the maximum tolerated dose (MTD). Such studies are important from a scientific and ethical perspective as they are used to make decisions on progression of potential candidate drugs, and to set dose levels for subsequent regulatory studies. The MTD is usually determined by parameters such as clinical signs, reductions in body weight and food consumption. However, these assessments are often subjective and there are no published criteria to guide the selection of an appropriate MTD. Even where an objective measurement exists, such as body weight loss (BWL), there is no agreement on what level constitutes an MTD. A global initiative including 15 companies, led by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), has shared data on BWL in toxicity studies to assess the impact on the animal and the study outcome. Information on 151 studies has been used to develop an alert/warning system for BWL in short term toxicity studies. The data analysis supports BWL limits for short term dosing (up to 7days) of 10% for rat and dog and 6% for non-human primates (NHPs).

  4. ANIMAL MODELS FOR STUDYING MISCARRIAGE: ILLUSTRATION WITH STUDY OF DRINKING WATER DISINFECTION BY-PRODUCTS

    Science.gov (United States)

    Animal models for studying miscarriage: Illustration with study of drinking water disinfection by-productsAuthors & affiliations:Narotsky1, M.G. and S. Bielmeier Laffan2.1Reproductive Toxicology Division, NHEERL, ORD, U.S. Environmental Protection Agency, Research Tri...

  5. Toxicity assessment of hydrazine fuels

    Energy Technology Data Exchange (ETDEWEB)

    Keller, W.C.

    1988-11-01

    The major health aspects of exposure to hydrazine propellants are reviewed. Toxic effects of hydrazine fuels on humans and animals as well as in vitro studies are discussed with emphasis on recent findings and USAF studies. Propellant hydrazines have been found to be genotoxic in in vitro studies and oncogenic in animal studies. Embryotoxicity has been demonstrated at very high exposures but not at occupationally encountered levels for hydrazine and unsymmetrical dimethylhydrazine. Epidemiologic evidence to support these findings is lacking; however, the results of animal and in vitro studies have resulted in lowering both the time-weighted average-threshold limit values and short-term exposure limits for these propellants.

  6. Toxicity evaluation of petroleum blending streams: inhalation subchronic toxicity/neurotoxicity study of a light catalytic reformed naphtha distillate in rats.

    Science.gov (United States)

    Schreiner, C; Bui, Q; Breglia, R; Burnett, D; Koschier, F; Lapadula, E; Podhasky, P; White, R

    2000-08-11

    A 13-wk whole-body inhalation study was conducted with Sprague-Dawley CD rats (16/sex/group) exposed to a light catalytic reformed naphtha distillate (LCRN-D, CAS number 64741-63-5) at target concentrations of 0, 750, 2500, and 7500 ppm for 6 h/d, 5 d/wk. Sixteen rats per sex in the control and high-dose groups were maintained after final exposure for a 4-wk recovery period. The highest exposure concentration was 75% of the lower explosive limit. Standard parameters of subchronic toxicity were measured throughout the study; at necropsy, organs were weighed and tissues processed for microscopic evaluation. Neurotoxicity evaluations consisted of motor activity (MA) and a functional operational battery (FOB) measured pretest, throughout exposure and after the recovery period. Neuropathology was evaluated at termination. No test-related mortality or effects on physical signs, body weight, food consumption, or clinical chemistry were observed. In males exposed to 7500-ppm LCRN-D, a statistically significant decrease in white blood cell counts and lymphocyte counts was observed at the termination of exposure that was not present in animals after the 4-wk recovery period. However, mean corpuscular volume was slightly decreased in high-dose males after the recovery period. Statistically significant increases in kidney weights relative to body weights in 7500-ppm male rats correlated with microscopically observed hyaline droplet formation and renal tubule dilation, indicative of light hydrocarbon nephropathy, a condition in male rats that is not toxicologically significant for humans. Statistically significant decrease in absolute and relative spleen weights in 7500-ppm male rats correlated with decreases in hematologic parameters but had no microscopic correlate and was not observed in animals after 4 wk of recovery. This mild, reversible effect in white blood cell populations may relate to the presence of aromatics in the distillate. The only effect of LCRN-D on

  7. Whole effluent toxicity of agricultural irrigation drainwater entering Stillwater National Wildlife Refuge, NV : Acute toxicity studies with fish and aquatic invertebrates

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This report covers the acute toxicity studies conducted with samples collected from Stillwater National Wildlife Refuge. The objective of these studies was to...

  8. Studies of the developmental toxicity of polycarboxylate dispersing agents.

    Science.gov (United States)

    Nolen, G A; Monroe, A; Hassall, C D; Iavicoli, J; Jamieson, R A; Daston, G P

    1989-06-01

    Three linear polycarboxylate compounds, two linear polyacrylates (90,000 MW and 4,500 MW) and one linear polyacrylate-maleate copolymer (12,000 MW), were tested for their teratogenic potential in female Sprague Dawley rats. These polymers, which were tested as sodium salts, are used as dispersing agents in detergent formulations at levels of 1-5%. All compounds were administered by gavage during organogenesis (days 6-15 of pregnancy). No adverse effects on development were seen with any of the three compounds at any of the doses tested. The highest dose, and therefore the minimum no-effect dose, for the three linear polymers was 1125 mg/kg/day for the 90,000 MW polyacrylate, 3000 mg/kg/day for the 4,500 MW polyacrylate, and 6670 mg/kg/day for the polyacrylate-maleate copolymer. Based on these data, these compounds are not developmentally toxic, even at very high dose levels.

  9. Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

    Energy Technology Data Exchange (ETDEWEB)

    Chapet, Olivier, E-mail: olivier.chapet@chu-lyon.fr [Department of Radiation Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); EMR3738, Université Lyon 1, Lyon (France); Decullier, Evelyne; Bin, Sylvie [Pole Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Lyon (France); Université Lyon 1, Lyon (France); EA SIS, Université de Lyon, Lyon (France); Faix, Antoine [Department of Urology, Clinique Beausoleil, Montpellier (France); Ruffion, Alain [Université Lyon 1, Lyon (France); Department of Urology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Jalade, Patrice [Department of Medical Physics, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Fenoglietto, Pascal [Department of Radiation Oncology and Physics, Institut du Cancer de Montpellier, Montpellier (France); Udrescu, Corina; Enachescu, Ciprian [Department of Radiation Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Azria, David [Department of Radiation Oncology and Physics, Institut du Cancer de Montpellier, Montpellier (France)

    2015-03-15

    Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.

  10. Chronic Toxicity Study of 'I'he Effect of Crude Petroleum (Bonny ...

    African Journals Online (AJOL)

    Chronic Toxicity Study of 'I'he Effect of Crude Petroleum (Bonny Light), Kerosine and ... Blood Cell Counts (WBC) were used to assess the etlect of crude oil (bony light) .... some Aquatic Organism Chemical and Institution of ... communities.

  11. Acute and sub acute toxicity and efficacy studies of Hippophae rhamnoides based herbal antioxidant supplement

    Directory of Open Access Journals (Sweden)

    Rashid Ali

    2012-01-01

    Conclusion: The data obtained indicate no toxicity of this antioxidant supplement up to the highest dose studied. Efficacy in terms of increased bioavailability of vitamin A and C in human volunteers indicates the clinical usefulness of the supplement.

  12. Webinar Presentation: Epidemiologic Studies of the Effects of Toxic Exposures on Brain and Behavior: Neuropsychological Assessment

    Science.gov (United States)

    This presentation, Epidemiologic Studies of the Effects of Toxic Exposures on Brain and Behavior: Neuropsychological Assessment, was given at the NIEHS/EPA Children's Centers 2015 Webinar Series: Interdisciplinary Approaches to Neurodevelopment.

  13. Study of gastrointestinal toxicity of selective COX-2 inhibitors in comparison with conventional NSAIDs

    Directory of Open Access Journals (Sweden)

    Hima Bindu K.

    2016-12-01

    Conclusions: In our short-term study, selective COX-2 inhibitors did not show any advantage over non-selective NSAIDs regarding their gastrointestinal toxicity. [Int J Res Med Sci 2016; 4(12.000: 5180-5184

  14. A Study on the Effects and Toxicity of Tranquil in Experimental Animals

    Institute of Scientific and Technical Information of China (English)

    唐玲芳; 宋玲; 张珍玲; 杨永年

    1999-01-01

    IntroductionMajorityofthecurrentlyusedsedativesareoraltabletsandareeasytoincurtoxicefectswhenoverdosed.Forinstance,diazepampo...

  15. STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS

    Science.gov (United States)

    Landsteiner, K.; Di Somma, A. A.

    1940-01-01

    Sensitization of guinea pigs to picric acid was obtained by application of oil solutions to the skin, preferably on inflamed sites or by treatment with a compound of picric acid with n-butyl-p-aminobenzoate. The lesions obtained in sensitive animals on superficial administration bore resemblance to human eczema. It seems probable that picric acid sensitization is an instance where a substance does not sensitize directly but after conversion into a more reactive compound, a principle which should be of wider application to instances where the original substance does not readily form conjugates. PMID:19871030

  16. Established patterns of animal study design undermine translation of disease-modifying therapies for Parkinson’s disease

    Science.gov (United States)

    Zeiss, Caroline J.; Allore, Heather G.; Beck, Amanda P.

    2017-01-01

    Translation of disease-modifying therapies in neurodegenerative disease has been disappointing. Parkinson’s disease (PD) was used to compare patterns of preclinical study design for symptomatic and potentially disease-modifying interventions. We examined the relationship of model, intervention type and timing, outcomes and outcome measures in 543 animal and human studies (1973–2015) across a contemporary cohort of animal and human interventional studies (n = 445), animal studies for approved interventions (n = 28), animal and human studies for those that failed to translate (n = 70). Detailed study design data were collected for 216 studies in non-human primate (NHP) and rodent toxin-induced models. Species-specific patterns of study design prevailed regardless of whether interventions were symptomatic or potentially disease-modifying. In humans and NHPs, interventions were typically given to both sexes well after the PD phenotype was established, and clinical outcome measures were collected at single (symptomatic) or multiple (disease-modifying) time-points. In rodents, interventions often preceded induction of the model, acute toxic protocols were common, usually given to young males, clinical outcome measures were used less commonly, and outcomes were less commonly assessed at multiple time points. These patterns were more prevalent in mice than rats. In contrast, study design factors such as randomization and blinding did not differ appreciably across symptomatic and disease-modifying intervention categories. The translational gap for potentially disease-modifying interventions in PD in part results from study designs, particularly in mice, that fail to model the progressive nature and relatively late intervention characteristic of PD, or that anchor mechanistic and neuropathologic data to longitudinal clinical outcomes. Even if measures to improve reproducibility are broadly adopted, perpetuation of these norms will continue to impede effective translation

  17. Antagonistic effects of Spirulina platensis against sub-acute deltamethrin toxicity in mice: Biochemical and histopathological studies.

    Science.gov (United States)

    Abdel-Daim, Mohamed; El-Bialy, Badr E; Rahman, Haidy G Abdel; Radi, Abeer M; Hefny, Hany A; Hassan, Ahmed M

    2016-02-01

    Spirulina platensis (SP); a microalga with high antioxidant and anti-inflammatory activities, acts as a food supplement in human and as many animal species. Deltamethrin (DLM) is a synthetic pyrethroid with broad spectrum activities against acaricides and insects and widely used for veterinary and agricultural purposes. Exposure to DLM leads to hepatotoxic, nephrotoxic and neurotoxic side effects for human and many species, including birds and fish. The present study was undertaken to examine the potential hepatoprotective, nephroprotective, neuroprotective and antioxidant effects of SP against sub-acute DLM toxicity in male mice. DLM intoxicated animals revealed a significant increase in serum hepatic and renal injury biomarkers as well as TNF-α level and AChE activity. Moreover, liver, kidney and brain lipid peroxidation and oxidative stress markers were altered due to DLM toxicity. Spirulina normalized the altered serum levels of AST, ALT, APL, LDH, γ-GT, cholesterol, uric acid, urea, creatinine AChE and TNF-α. Furthermore, it reduced DLM-induced tissue lipid peroxidation, nitric oxide and oxidative stress in a dose-dependent manner. Collectively, that Spirulina supplementation could overcome DLM-induced hepatotoxicty, nephrotoxicity and neurotoxicity by abolishing oxidative tissue injuries.

  18. Cardiotoxicity and apoptotic activity in subacute endosulfan toxicity and the protective effect of vitamin C in rabbits: a pathological study.

    Science.gov (United States)

    Ozmen, Ozlem

    2013-01-01

    Cardiovascular disease is one of the most significant causes of mortality in humans and animals, and its etiology is usually unknown. The aim of this study was to investigate the cardiac pathology of endosulfan toxicity and the protective effect of vitamin C in rabbits. Twenty-four rabbits were divided into 4 groups: (1) the END group was given a daily sublethal dose of endosulfan in corn oil by oral gavage for 6 weeks; (2) the END + C group received the endosulfan as well as vitamin C over the same 6-week period; (3) the OIL + C group received corn oil daily and vitamin C every other day; and (4) the OIL group received only corn oil daily. We observed microscopic hemorrhages, single-cell necrosis, inflammatory reactions, and fibrotic changes in the myocardium in the END group. Small hemorrhages and single-cell necrosis also were seen in some hearts in the END + C group, but no inflammation was observed. Caspase-3 immunoreactivity was more significant in myocardial cells in the END group compared with the others. A protective effect of vitamin C on lesions was observed in the END + C group. These results showed that endosulfan resulted in toxic changes in the hearts of rabbits, but this toxicity could be decreased with vitamin C treatment.

  19. Toxicity evaluation of petroleum blending streams: inhalation subchronic toxicity/neurotoxicity study of a light alkylate naphtha distillate in rats.

    Science.gov (United States)

    Schreiner, C; Lapadula, E; Breglia, R; Bui, Q; Burnett, D; Koschier, F; Podhasky, P; White, R; Mandella, R; Hoffman, G

    1998-10-23

    A 13-wk inhalation study was conducted with Sprague-Dawley CD rats (12/sex/group) were exposed by inhalation for 13 weeks to a light alkylate naphtha distillate (LAND-2, C4-C10; average molecular weight 89.2) at actual average concentrations of 0 (room air), 668, 2220, or 6646 ppm, 6 h/d, 5 d/wk; 12 additional rats/sex in the control and high dose groups were held after final exposure for a 4-wk recovery period. The highest exposure concentration was 75% of the lower explosive limit. Standard parameters of subchronic toxicity were measured throughout the study; at necropsy, organs were weighed and tissues processed for microscopic evaluation. Neurotoxicity evaluations consisted of motor activity (MA) and a functional operational battery (FOB) measured pretest, during 5, 9, and 14 wk of the study, and after the 4-wk recovery period. Whole-body perfusion and microscopic examination of selected organs and nervous tissue from the control and high dose rats were conducted at the end of exposure. No test-related mortality or effects on physical signs, body weight, or food consumption were observed. Statistically significant increases in absolute and relative kidney weights in high-exposure males correlated with microscopically observed hyaline droplet formation and renal nephropathy, effects in male rats that are not toxicologically significant for humans. Increased liver weights in both sexes at the highest dose had no microscopic correlate and appeared reversible after the 4-wk recovery period. Exposure to LAND-2 at any dose did not produce neurotoxicity measured by MA, FOB, or neuropathology. The no-observed-effects level (NOEL) for LAND-2 was 2220 ppm for subchronic toxicity and > or =26646 ppm for neurotoxicity.

  20. Predictive Factors of Radiation-Induced Lung Toxicity in Lung Cancer Patients: A Retrospective Study

    Directory of Open Access Journals (Sweden)

    Maher Soliman

    2016-07-01

    Full Text Available Background: Radiation-induced lung toxicity is an important dose-limiting toxicity in lung cancer radiotherapy, for which there are no generally accepted predictive factors. This study seeks to identify risk factors associated with the development of severe radiation-induced lung toxicity using clinical and dosimetric parameters. Methods: We reviewed the medical records of 54 patients with histologically proven stage III non-small cell lung cancer treated with three dimensional-conformal radiotherapy at Alexandria Main University Hospital between January 2008 and December 2011. The original treatment plans for those patients were restored and imported to a treatment planning system. Lung dose–volume histograms and various dosimetric parameters were calculated. Univariate and multivariate logistic regression analyses were performed. Results: The following grades of radiation-induced lung toxicity were observed in patients - grade 0: 17 (31.5%, grade 1: 5 (9.3%, grade 2: 13 (24.1%, grade 3: 15 (27.8%, and grade 5: 4 (7.4%. A total of 19 (35.2% patients developed grade ≥3 and were considered to have an event. Univariate analysis showed that age, presence of chronic obstructive pulmonary disease and location of the primary tumor had significant associations with severe radiation-induced lung toxicity. Other dosimetric variables such as tumor side, histology, forced expiratory volume in 1 s, smoking, and gender showed no significant correlations with severe radiation-induced lung toxicity. Multivariate analysis showed that the presence of chronic obstructive pulmonary disease (P=0.001 and location of the primary tumor (P=0.010 were the only predictive factors for severe radiation-induced lung toxicity. Conclusion: This study demonstrates that patients with chronic obstructive pulmonary disease and lower lung lobe tumors have a high risk of severe radiationinduced lung toxicity when treated with combined chemoradiotherapy. These easily obtained

  1. Biodistribution and toxicity of engineered gold nanoparticles: a review of in vitro and in vivo studies.

    Science.gov (United States)

    Khlebtsov, Nikolai; Dykman, Lev

    2011-03-01

    Recent advances in wet chemical synthesis and biomolecular functionalization of gold nanoparticles have led to a dramatic expansion of their potential biomedical applications, including biosensorics, bioimaging, photothermal therapy, and targeted drug delivery. As the range of gold nanoparticle types and their applications continues to increase, human safety concerns are gaining attention, which makes it necessary to better understand the potential toxicity hazards of these novel materials. Whereas about 80 reports on the in vivo biodistribution and in vitro cell toxicity of gold nanoparticles are available in the literature, there is lack of correlation between both fields and there is no clear understanding of intrinsic nanoparticle effects. At present, the major obstacle is the significant discrepancy in experimental conditions under which biodistribution and toxicity effects have been evaluated. This critical review presents a detailed analysis of data on the in vitro and in vivo biodistribution and toxicity of most popular gold nanoparticles, including atomic clusters and colloidal particles of diameters from 1 to 200 nm, gold nanoshells, nanorods, and nanowires. Emphasis is placed on the systematization of data over particle types and parameters, particle surface functionalization, animal and cell models, organs examined, doses applied, the type of particle administration and the time of examination, assays for evaluating gold particle toxicity, and methods for determining the gold concentration in organs and distribution of particles over cells. On the basis of a critical analysis of data, we arrive at some general conclusions on key nanoparticle parameters, methods of particle surface modification, and doses administered that determine the type and kinetics of biodistribution and toxicity at cellular and organismal levels (197 references).

  2. Comparison of toxicity values across zebrafish early life stages and mammalian studies: Implications for chemical testing.

    Science.gov (United States)

    Ducharme, Nicole A; Reif, David M; Gustafsson, Jan-Ake; Bondesson, Maria

    2015-08-01

    With the high cost and slow pace of toxicity testing in mammals, the vertebrate zebrafish has become a tractable model organism for high throughput toxicity testing. We present here a meta-analysis of 600 chemicals tested for toxicity in zebrafish embryos and larvae. Nineteen aggregated and 57 individual toxicity endpoints were recorded from published studies yielding 2695 unique data points. These data points were compared to lethality and reproductive toxicology endpoints analyzed in rodents and rabbits and to exposure values for humans. We show that although many zebrafish endpoints did not correlate to rodent or rabbit acute toxicity data, zebrafish could be used to accurately predict relative acute toxicity through the rat inhalation, rabbit dermal, and rat oral exposure routes. Ranking of the chemicals based on toxicity and teratogenicity in zebrafish, as well as human exposure levels, revealed that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), benzo(a)pyrene, and chlorpyrifos ranked in the top nine of all chemicals for these three categories, and as such should be considered high priority chemicals for testing in higher vertebrates.

  3. Toxicity evaluation of 2-hydroxybiphenyl and other compounds involved in studies of fossil fuels biodesulphurisation.

    Science.gov (United States)

    Alves, L; Paixão, S M

    2011-10-01

    The acute toxicity of some compounds used in fossil fuels biodesulphurisation studies, on the respiration activity, was evaluated by Gordonia alkanivorans and Rhodococcus erythropolis. Moreover, the effect of 2-hydroxybiphenyl on cell growth of both strains was also determined, using batch (chronic bioassays) and continuous cultures. The IC₅₀ values obtained showed the toxicity of all the compounds tested to both strains, specially the high toxicity of 2-HBP. These results were confirmed by the chronic toxicity data. The toxicity data sets highlight for a higher sensitivity to the toxicant by the strain presenting a lower growth rate, due to a lower cells number in contact with the toxicant. Thus, microorganisms exhibiting faster generation times could be more resistant to 2-HBP accumulation during a BDS process. The physiological response of both strains to 2-HBP pulse in a steady-state continuous culture shows their potential to be used in a future fossil fuel BDS process. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Toward an Understanding of Human Violence: Cultural Studies, Animal Studies, and the Promise of Posthumanism

    Science.gov (United States)

    Worsham, Lynn

    2013-01-01

    On January 3, 2012, the "New York Times" featured an article announcing the emergence of the new interdisciplinary field of animal studies, which is spreading across college campuses in new course offerings, new majors, and new undergraduate and graduate programs. This new field grows out of, on the one hand, a long history of scientific research…

  5. Rebaudioside A: two-generation reproductive toxicity study in rats.

    Science.gov (United States)

    Curry, Leslie L; Roberts, Ashley; Brown, Nigel

    2008-07-01

    Rebaudioside A was administered via the diet to male and female Han Wistar rats at 0, 7500, 12,500, and 25,000ppm for two generations. Rebaudioside A treatment was not associated with any signs of clinical toxicity or adverse effects on body weight, body weight gain, or food consumption. No treatment-related effects of rebaudioside A were observed in either the F0 or F1 generations on reproductive performance parameters including mating performance, fertility, gestation lengths, oestrous cycles, or sperm motility, concentration, or morphology. The survival and general condition of the F1 and F2 offspring, their pre-weaning reflex development, overall body weight gains, and the timing of sexual maturation, were not adversely affected by rebaudioside A treatment. The NOAEL for reproductive effects was 25,000ppm and the NOAEL for the survival, development, and general condition of the offspring also was considered to be 25,000ppm or 2048-2273mg/kg body weight/day.

  6. Recent progress in the study of intracellular toxicity of amyloid β peptide in Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yan; YU Longchuan

    2007-01-01

    Amyloid β (Aβ) deposition is one of the major pathological markers of Alzheimer's disease (AD). Extracellular Aβ toxicity has been studied for a long time in AD research field. However, controversial data show that extracellular Aβ load does not correlate with the dementia levels of AD patients and extracellular Aβ only induces significant cell death at non-physiological high concentrations.With the evolvement of Aβ hypothesis, considerable attention has been devoted to the study of intracellular Aβ toxicity recently. Intracellular Aβ induces dramatic cell loss in AD transgenic models and in human primary neurons (at pM concentrations) through p53, Bax and caspase-6 pathways. Here, we review the generation, toxicity and possible pathways of intracellular Aβ toxicity, and discuss the implication and current knowledge of intracellular Aβ in neuronal cell loss in neurodegenerative diseases.

  7. Ozonides: intermediates in ozone-induced toxicity. A study on their mechanism of toxic action and detoxification by antioxidants

    NARCIS (Netherlands)

    Hempenius, R.A.

    2000-01-01

    Ozone is a major constituent of photochemical smog. The toxicity of ozone is well documented and has been related to its strong oxidative potential. The principal target organ for ozone toxicity is the respiratory system. Unsaturated fatty acids, which are present in both the lipids of the lung lini

  8. In vivo toxicity studies on gall extracts of Terminalia chebula (Gaertn. Retz. (combretaceae

    Directory of Open Access Journals (Sweden)

    Ravi Shankara Birur Eshwarappa

    2016-01-01

    The present study investigates the toxicity effect of different extracts of galls of T. chebulla, which would serve as an index for formulation of drugs for treatment of various diseases. Presumably, these activities could be attributed in part to the polyphenolic features of the extract, as there was a strong correlation of higher toxic effect with that of high total phenolic and flavonoids content in the ethanolic leaf gall extracts of T. chebula.

  9. Harbour sediment toxicity: An italian case study; Valutazione della tossicita` di sedimenti portuali

    Energy Technology Data Exchange (ETDEWEB)

    Pellegrini, M. [ICRAM, Istituto Centrale per la -ricerca Scientifica e Tecnologica Applicata al Mare, Rome (Italy); Bigongiari, N.; Mellera, F.; Giuliani, S. [CIBM, Centro Interuniversitario di Biologia Marina, Livorno (Italy); De Poorter, L. R. M. [AquaSense Consultants, Amsterdam (Netherlands)

    1998-01-01

    Harbour sediments usually contain a complex mixture of compounds originating from industrial and shipping activities. An important tool for the recognition of potential toxic effects of sediments is the use of bioassays. In order to estimate harbour sediment toxicity a specific study was carried out measuring reduction of microbial luminescence (Vibrio fischeri), oyster larvae development impairment (Crassostrea gigas) and amphipod mortality (Corophium volutator). Bioassay results are correlated with data on chemical contaminants (heavy metals, PAHs and PCBs).

  10. Anti-inflammatory and toxicity studies of atranorin extracted from Cladina kalbii Ahti in rodents

    Directory of Open Access Journals (Sweden)

    Marcelia Garcez Dória de Melo

    2011-12-01

    Full Text Available Atranorin (ATR is the main compound from the lichen Cladina kalbii Ahti, which grows in the arid regions of northeastern Brazil. This study was conducted to evaluate the anti-inflammatory and toxicological properties of ATR. To evaluate anti-inflammatory properties, paw edema was induced by injecting 0.1 mL of carrageenan into the subplantar region of the right hind paw of rats, and leukocyte migration was induced by injection of 500 µL of carrageenan into the peritoneal cavity of mice. In addition, we determined ATR cytotoxicity in L929 cells by MTT assay and acute (5 g/kg-single dose and subchronic (50 mg/kg-30 days toxicity tests in Wistar rats. The results showed that ATR (100 mg/kg and 200 mg/kg exhibited significant anti-inflammatory activity (paw edema and leukocyte migration. In the acute toxicity test, the animals showed hypoactivity and lethargy during the initial period (first 6 hours and increase in total protein, total and indirect bilirubin, and alkaline phosphatase after 14 days in ATR-treated male rats. The subchronic toxicity test revealed increases in total protein, globulin, gamma-glutamyl transferase, alkaline phosphatase, and total and direct bilirubin in ATR-treated female rats. Histological analysis revealed no changes in the architecture and morphology of the organs. These results suggest that ATR has significant anti-inflammatory activity, with no significant acute and subchronic toxicity or cytotoxicity.Atranorina (ATR é o principal composto do líquen Cladina kalbii Ahti, que cresce em terras áridas do nordeste brasileiro. Este estudo foi realizado para avaliar as propriedades antiinflamatórias e toxicológicas da ATR. Para avaliar as propriedades antiinflamatórias, o edema de pata foi induzido, administrando-se 0,1 mL de carragenina na região subplantar da pata traseira direita e a migração leucocitária foi induzida pela injeção de 500 µL de carragenina no peritônio. Além disso, determinou-se a

  11. Nanosilica and Polyacrylate/Nanosilica: A Comparative Study of Acute Toxicity

    Directory of Open Access Journals (Sweden)

    Ying-Mei Niu

    2016-01-01

    Full Text Available We compared the acute toxicity of nanosilica and polyacrylate/nanosilica instillation in Wistar rats (n=60. Exposure to nanosilica and polyacrylate/nanosilica showed a 30% mortality rate. When compared with saline-treated rats, animals in both exposure groups exhibited a significant reduction of PO2 (P<0.05 at both 24 and 72 hr. after exposure. Both exposure groups exhibited a significant reduction of neutrophils in arterial blood compared to saline controls (P<0.05 24 hr. after exposure. The levels of blood ALT and LDH in exposed groups were found to be significantly increased (P<0.05 24 hr. following exposure. The exposed groups exhibited various degrees of pleural effusion and pericardial effusion. Our findings indicated respiratory exposure to polyacrylate/nanosilica and nanosilica is likely to cause multiple organ toxicity.

  12. Comparative virulence studies and transcriptome analysis of Staphylococcus aureus strains isolated from animals

    OpenAIRE

    Zahid Iqbal; Seleem, Mohamed N.; Hafiz Iftikhar Hussain; Lingli Huang; Haihong Hao; Zonghui Yuan

    2016-01-01

    Several studies have been conducted to check the prevalence of methicillin-resistant strains of Staphylococcus aureus (MRSA) in animals and animal-derived food products but limited data are available regarding their virulence and associated gene expression profile. In the present study, antibiotic resistance and virulence of MRSA and methicillin-sensitive S. aureus animal isolates were determined in vitro by agar dilution, biofilm formation, adhesion, invasion and intracellular survivability ...

  13. Acute and sub chronic toxicity study of aqueous extract from the leaves and branches of Campomanesia velutina (Cambess) O. Berg.

    Science.gov (United States)

    Araújo, Marcela Carolina de Paula Michel; Barcellos, Neila Márcia Silva; Vieira, Paula Melo de Abreu; Gouveia, Thiago Magalhães; Guerra, Martha Oliveira; Peters, Vera Maria; Saúde-Guimarães, Dênia Antunes

    2017-04-06

    Campomanesia velutina leaves and branches infusions are used in Brazilian folk medicine to treat diarrhea and to ameliorate intestinal cramps, respectively. Carry out the acute and sub chronic pre-clinical evaluation and thus assess the safety and toxicological potential of the specie. In vivo toxicity was evaluated by acute and sub chronic toxicity assays conducted according to the guidelines of the Brazilian Agency of National Health Surveillance (Agência Nacional de Vigilância Sanitária - ANVISA). For acute toxicity evaluation, a single dose of aqueous extracts from the leaves (AEL) and branches (AEB) of Campomanesia velutina were orally administered to mice at doses of 300, 600 and 1200mg/kg. Then, the animals were observed for 14 days. In the sub chronic study, the extracts were orally administered to mice for 14 days at doses of 300, 600 and 1200mg/kg. To assess the toxicological effects, animals were closely observed on general behavior, clinical signs of toxicity, body weight, food and water intake. At the end of the experiment, it was performed biochemical and hematological evaluations, as well as histopathological analysis from the following organs: brain, heart, lungs, liver, stomach, small intestine (section) and left kidney. Preliminary phytochemical analysis was performed using thin layer chromatography (TLC) and colorimetric pharmacognostic tests. In oral acute assay, treatment with AEB at the major dose (1200mg/kg) caused diarrhea, abdominal cramps and tremors in females. These effects were reversed at 4th hour. Normochromic normocytic anemia was observed in males treated with AEL 300mg/kg and AEB 600 and 1200mg/kg as well as in females treated with AEB 300 and 1200mg/kg. The kidney of all treated animals showed moderate inflammation and a few hemorrhagic points. In sub chronic assay, treatment with AEL 600mg/kg, AEL 1200mg/kg and AEB 1200mg/kg caused hyper excitability in females that was not reversed. Treatments also had impact on weight gain

  14. Zinc oxide nanoparticles: a 90-day repeated-dose dermal toxicity study in rats

    Directory of Open Access Journals (Sweden)

    Ryu HJ

    2014-12-01

    Full Text Available Hwa Jung Ryu,1,* Mu Yeb Seo,2,* Sung Kyu Jung,1 Eun Ho Maeng,2 Seung-Young Lee,2 Dong-Hyouk Jang,2 Taek-Jin Lee,2 Ki-Yeon Jo,2 Yu-Ri Kim,3 Kyu-Bong Cho,4 Meyoung-Kon Kim,3 Beom Jun Lee,5 Sang Wook Son1 1Department of Dermatology, Korea University College of Medicine, Seoul, 2Korea Testing and Research Institute, Gyunggido, 3Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, 4Department of Clinical Laboratory Science, Shinheung College, Uijeongbu, 5College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea *These authors contributed equally to this work and both should be considered first authors Abstract: Zinc oxide (ZnO works as a long-lasting, broad-spectrum physical sunblock, and can prevent skin cancer, sunburn, and photoaging. Nanosized ZnO particles are used often in sunscreens due to consumer preference over larger sizes, which appear opaque when dermally applied. Although the US Food and Drug Administration approved the use of nanoparticles (NPs in sunscreens in 1999, there are ongoing safety concerns. The aim of this study was to evaluate the subchronic toxicity of ZnO NPs after dermal application according to the Organization for Economic Cooperation and Development Test Guidelines 411 using Good Laboratory Practice. Sprague Dawley rats were randomly divided into eight (one control, one vehicle control, three experimental, and three recovery groups. Different concentrations of ZnO NPs were dermally applied to the rats in the experimental groups for 90 days. Clinical observations as well as weight and food consumption were measured and recorded daily. Hematology and biochemistry parameters were determined. Gross pathologic and histopathologic examinations were performed on selected tissues from all animals. Analyses of tissue were undertaken to determine target organ tissue distribution. There was no increased mortality in the experimental group. Although there

  15. A search filter for increasing the retrieval of animal studies in Embase.

    Science.gov (United States)

    de Vries, Rob B M; Hooijmans, Carlijn R; Tillema, Alice; Leenaars, Marlies; Ritskes-Hoitinga, Merel

    2011-10-01

    Collecting and analysing all available literature before starting a new animal experiment is important and it is indispensable when writing systematic reviews of animal research. In practice, finding all animal studies relevant to a specific research question turns out to be anything but simple. In order to facilitate this search process, we previously developed a search filter for retrieving animal studies in the most often used biomedical database, PubMed. It is a general requirement for systematic reviews, however, that at least two databases are searched. In this report, we therefore present a similar search filter for a second important database, namely Embase. We show that our filter retrieves more animal studies than (a combination of) the options currently available in Embase. Our search filters for PubMed and Embase therefore represent valuable tools for improving the quality of (systematic) reviews and thereby of new animal experiments.

  16. Quantitative structure-toxicity relationship study of some natural and synthetic coumarins using retention parameters

    Directory of Open Access Journals (Sweden)

    Rabtti El Hadi M.A.

    2012-01-01

    Full Text Available Four lipophilicity descriptors (RM0, b, C0, PC1 for twelve coumarine derivatives were determined by reversed-phase thin-layer chromatography in order to analyze which descriptor best describes the lipophilicity of coumarines investigated. Moreover, possible chemical toxicity of coumarins, expressed as the probability of a compound to cause organ-specific health effects, was calculated using ACD/Tox Suite program. The quantitative relationships between toxicity and molecular descriptors, including experimentally determined lipophilicity descriptors obtained in current study, were investigated using partial least square regression. The best models were obtained for kidney and liver health effects. Quantitative structure-toxicity relationship models revealed the importance of electric polarization descriptors, size descriptors and lipophilicity descriptors. Obtained models were used for the selection of the structural features of the compounds that are significantly affecting their absorption, distribution, metabolism, excretion, and toxicity. [Acknowledgements. This work has been supported by the Ministry of Education and Science of Serbia, Grant 172017.

  17. U.S./Mexico Border environmental study toxics release inventory data, 1988--1992

    Energy Technology Data Exchange (ETDEWEB)

    O`Brien, R.F.; LoPresti, C.A.

    1996-02-01

    This is a report on industrial toxic chemical releases and transfers based on information reported to the Toxics Release Inventory (TRI), a database maintained by the USEPA. This document discusses patterns of toxic chemical releases to the atmosphere, to water, to the land, and to underground injection; and transfers of toxic chemicals to Publicly Owned Treatment Works (POTW), and for disposal, treatment and other off-site transfers during the TRI reporting years 1988--1992. Geographic coverage is limited to the US side of the ``Border Area``, the geographic area situated within 100 km of the US/Mexico international boundary. A primary purpose of this study is to provide background information that can be used in the future development of potential ``indicator variables`` for tracking environmental and public health status in the Border Area in conjunction with the implementation of the North American Free Trade Agreement (NAFTA).

  18. Standardized Total Average Toxicity Score: A Scale- and Grade-Independent Measure of Late Radiotherapy Toxicity to Facilitate Pooling of Data From Different Studies

    Energy Technology Data Exchange (ETDEWEB)

    Barnett, Gillian C., E-mail: gillbarnett@doctors.org.uk [University of Cambridge Department of Oncology, Oncology Centre, Cambridge (United Kingdom); Cancer Research-UK Centre for Genetic Epidemiology and Department of Oncology, Strangeways Research Laboratories, Cambridge (United Kingdom); West, Catharine M.L. [School of Cancer and Enabling Sciences, Manchester Academic Health Science Centre, University of Manchester, Christie Hospital, Manchester (United Kingdom); Coles, Charlotte E. [University of Cambridge Department of Oncology, Oncology Centre, Cambridge (United Kingdom); Pharoah, Paul D.P. [Cancer Research-UK Centre for Genetic Epidemiology and Department of Oncology, Strangeways Research Laboratories, Cambridge (United Kingdom); Talbot, Christopher J. [Department of Genetics, University of Leicester, Leicester (United Kingdom); Elliott, Rebecca M. [School of Cancer and Enabling Sciences, Manchester Academic Health Science Centre, University of Manchester, Christie Hospital, Manchester (United Kingdom); Tanteles, George A. [Department of Clinical Genetics, University Hospitals of Leicester, Leicester (United Kingdom); Symonds, R. Paul [Department of Cancer Studies and Molecular Medicine, University Hospitals of Leicester, Leicester (United Kingdom); Wilkinson, Jennifer S. [University of Cambridge Department of Oncology, Oncology Centre, Cambridge (United Kingdom); Dunning, Alison M. [Cancer Research-UK Centre for Genetic Epidemiology and Department of Oncology, Strangeways Research Laboratories, Cambridge (United Kingdom); Burnet, Neil G. [University of Cambridge Department of Oncology, Oncology Centre, Cambridge (United Kingdom); Bentzen, Soren M. [University of Wisconsin, School of Medicine and Public Health, Department of Human Oncology, Madison, WI (United States)

    2012-03-01

    Purpose: The search for clinical and biologic biomarkers associated with late radiotherapy toxicity is hindered by the use of multiple and different endpoints from a variety of scoring systems, hampering comparisons across studies and pooling of data. We propose a novel metric, the Standardized Total Average Toxicity (STAT) score, to try to overcome these difficulties. Methods and Materials: STAT scores were derived for 1010 patients from the Cambridge breast intensity-modulated radiotherapy trial and 493 women from University Hospitals of Leicester. The sensitivity of the STAT score to detect differences between patient groups, stratified by factors known to influence late toxicity, was compared with that of individual endpoints. Analysis of residuals was used to quantify the effect of these covariates. Results: In the Cambridge cohort, STAT scores detected differences (p < 0.00005) between patients attributable to breast volume, surgical specimen weight, dosimetry, acute toxicity, radiation boost to tumor bed, postoperative infection, and smoking (p < 0.0002), with no loss of sensitivity over individual toxicity endpoints. Diabetes (p = 0.017), poor postoperative surgical cosmesis (p = 0.0036), use of chemotherapy (p = 0.0054), and increasing age (p = 0.041) were also associated with increased STAT score. When the Cambridge and Leicester datasets were combined, STAT was associated with smoking status (p < 0.00005), diabetes (p = 0.041), chemotherapy (p = 0.0008), and radiotherapy boost (p = 0.0001). STAT was independent of the toxicity scale used and was able to deal with missing data. There were correlations between residuals of the STAT score obtained using different toxicity scales (r > 0.86, p < 0.00005 for both datasets). Conclusions: The STAT score may be used to facilitate the analysis of overall late radiation toxicity, from multiple trials or centers, in studies of possible genetic and nongenetic determinants of radiotherapy toxicity.

  19. Comparative toxicity study of Ag, Au, and Ag-Au bimetallic nanoparticles on Daphnia magna.

    Science.gov (United States)

    Li, Ting; Albee, Brian; Alemayehu, Matti; Diaz, Rocio; Ingham, Leigha; Kamal, Shawn; Rodriguez, Maritza; Bishnoi, Sandra Whaley

    2010-09-01

    A comparative assessment of the 48-h acute toxicity of aqueous nanoparticles synthesized using the same methodology, including Au, Ag, and Ag-Au bimetallic nanoparticles, was conducted to determine their ecological effect in freshwater environments through the use of Daphnia magna, using their mortality as a toxicological endpoint. D. magna are one of the standard organisms used for ecotoxicity studies due to their sensitivity to chemical toxicants. Particle suspensions used in toxicity testing were well-characterized through a combination of absorbance measurements, atomic force or electron microscopy, flame atomic absorption spectrometry, and dynamic light scattering to determine composition, aggregation state, and particle size. The toxicity of all nanoparticles tested was found to be dose and composition dependent. The concentration of Au nanoparticles that killed 50% of the test organisms (LC(50)) ranged from 65-75 mg/L. In addition, three different sized Ag nanoparticles (diameters = 36, 52, and 66 nm) were studied to analyze the toxicological effects of particle size on D. magna; however, it was found that toxicity was not a function of size and ranged from 3-4 μg/L for all three sets of Ag nanoparticles tested. This was possibly due to the large degree of aggregation when these nanoparticles were suspended in standard synthetic freshwater. Moreover, the LC(50) values for Ag-Au bimetallic nanoparticles were found to be between that of Ag and Au but much closer to that of Ag. The bimetallic particles containing 80% Ag and 20% Au were found to have a significantly lower toxicity to Daphnia (LC(50) of 15 μg/L) compared to Ag nanoparticles, while the toxicity of the nanoparticles containing 20% Ag and 80% Au was greater than expected at 12 μg/L. The comparison results confirm that Ag nanoparticles were much more toxic than Au nanoparticles, and that the introduction of gold into silver nanoparticles may lower their environmental impact by lowering the amount

  20. The use of transgenic animals to study lipoprotein metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Rubin, E.M.; Plump, A.S.

    1993-12-01

    The application of transgenic technology to lipoprotein metabolism and atherosclerosis was first reported in 1988. Today, a large percentage of the genes involved in lipoprotein metabolism have been overexpressed in mice, and a substantial number of these same genes have been disrupted by homologous recombination in embryonic stem (ES) cells. The utility of animal models of lipoprotein metabolism and atherosclerosis is far-reaching given the complex nature of these systems. There are at least 17 known genes directly involved in lipoprotein metabolism and likely dozens more may be involved. This massive network of interacting factors has necessitated the development of in vivo systems which can be subject to genetic manipulation. The power of overexpression is obvious: elucidating function in a relatively controlled genetic environment in which the whole system is present and operational. The not-so-obvious problem with transgenics is ``background,`` or for purposes of the current discussion, the mouse`s own lipoprotein system. With the advent of gene knockout, we have been given the ability to overcome ``background.`` By recreating the genetic complement of the mouse we can alter a system in essentially any manner desired. As unique tools, and in combination with one another, the overexpression of foreign genes and the targeted disruption or alteration of endogenous genes has already and will continue to offer a wealth of information on the biology of lipoprotein metabolism and its effect on atherosclerosis susceptibility.

  1. Mitochondrial DNA damage and animal longevity: insights from comparative studies.

    Science.gov (United States)

    Pamplona, Reinald

    2011-03-02

    Chemical reactions in living cells are under strict enzyme control and conform to a tightly regulated metabolic program. However, uncontrolled and potentially deleterious endogenous reactions occur, even under physiological conditions. Aging, in this chemical context, could be viewed as an entropic process, the result of chemical side reactions that chronically and cumulatively degrade the function of biological systems. Mitochondria are a main source of reactive oxygen species (ROS) and chemical sidereactions in healthy aerobic tissues and are the only known extranuclear cellular organelles in animal cells that contain their own DNA (mtDNA). ROS can modify mtDNA directly at the sugar-phosphate backbone or at the bases, producing many different oxidatively modified purines and pyrimidines, as well as single and double strand breaks and DNA mutations. In this scenario, natural selection tends to decrease the mitochondrial ROS generation, the oxidative damage to mtDNA, and the mitochondrial mutation rate in long-lived species, in agreement with the mitochondrial oxidative stress theory of aging.

  2. Nanosilica and Polyacrylate/Nanosilica: A Comparative Study of Acute Toxicity

    OpenAIRE

    Ying-Mei Niu; Xiao-Li Zhu; Bing Chang; Zhao-Hui Tong; Wen Cao; Pei-Huan Qiao; Lin-Yuan Zhang; Jing Zhao; Yu-Guo Song

    2016-01-01

    We compared the acute toxicity of nanosilica and polyacrylate/nanosilica instillation in Wistar rats (n = 60). Exposure to nanosilica and polyacrylate/nanosilica showed a 30% mortality rate. When compared with saline-treated rats, animals in both exposure groups exhibited a significant reduction of PO2 (P < 0.05) at both 24 and 72 hr. after exposure. Both exposure groups exhibited a significant reduction of neutrophils in arterial blood compared to saline controls (P < 0.05) 24 hr. after expo...

  3. Juvenile animal studies for the development of paediatric medicines: a description and conclusions from a European Medicines Agency workshop on juvenile animal testing for nonclinical assessors.

    Science.gov (United States)

    Silva-Lima, Beatriz; Due Theilade-Thomsen, Mette; Carleer, Jacqueline; Vidal, Jean-Marc; Tomasi, Paolo; Saint-Raymond, Agnes

    2010-12-01

    A workshop organised by the European Medicines Agency involved assessors and experts present in a Nonclinical Working Group evaluating juvenile animal studies for Paediatric Investigation Plans in collaboration with the Paediatric Committee and the Safety Working Party of the Committee for Human Medicinal Products. The objective of the workshop was to analyse which juvenile animal studies proposals were received and agreed by the Paediatric Committee, to check consistency and how to apply the existing European guideline on juvenile animal studies. A comparison of main organ system development in man vs. animal species was presented to guide the review and to support species selection and protocol design. An analysis of juvenile animal studies included in finalised PIP's was also presented. Out of 109 paediatric investigation plans finalised between November 2008 and March 2009, 43 included one or more juvenile animal studies. In most cases the preferred species was the rat; one species only was requested to be studied (20/22), but in a minority two species were required (2/22). When deciding on the characteristics of the juvenile animal studies, such as age of animals at study start, the age of the children targeted by the medicine was considered. It is expected that the increasing experience gained by Applicants and Regulators will allow further refining the criteria for these juvenile animal studies. Further research on this topic is highly encouraged in the European Regulatory framework.

  4. Acute, reproductive toxicity and two-generation teratology studies of a standardized quassinoid-rich extract of Eurycoma longifolia Jack in Sprague-Dawley rats.

    Science.gov (United States)

    Low, Bin-Seng; Das, Prashanta Kumar; Chan, Kit-Lam

    2014-07-01

    The roots of Eurycoma longifolia Jack are popularly sought as herbal medicinal supplements to improve libido and general health amongst the local ethnic population. The major quassinoids of E. longifolia improved spermatogenesis and fertility but toxicity studies have not been well documented. The reproductive toxicity, two generation of foetus teratology and the up-and-down acute toxicity were investigated in Sprague-Dawley rats orally treated with quassinoid-rich E. longifolia extract (TAF273). The results showed that the median lethal dose (LD50 ) of TAF273 for female and male rats was 1293 and >2000 mg/kg, respectively. Fertility index and litter size of the TAF273 treated were significantly increased when compared with those of the non-treated animals. The TAF273-treated dams decreased in percentage of pre-implantation loss, post-implantation loss and late resorption. No toxic symptoms were observed on the TAF273-treated pregnant female rats and their foetuses were normal. The no-observed adverse effect level (NOAEL) obtained from reproductive toxicity and teratology studies of TAF273 in rats was 100 mg/kg body weight/day, being more than 10-fold lower than the LD50 value. Thus, any human dose derived from converting the rat doses of 100 mg/kg and below may be considered as safe for further clinical studies.

  5. Humans as an animal model? : studies on cue interaction, occasion setting, and context dependency

    NARCIS (Netherlands)

    Dibbets, Pauline

    2002-01-01

    The objective of the present thesis was to study human learning behaviour and to compare the results with those from animal learning studies. Three topics originating from animal learning research were examined: cue interaction, occasion setting, and context dependency. A series of experiments was f

  6. Empirical Studies of the Value of Algorithm Animation in Algorithm Understanding

    Science.gov (United States)

    1993-08-01

    A series of studies is presented using algorithm animation to teach computer algorithms . These studies are organized into three components: eliciting...lecture with experimenter-preprepared data sets. This work has implications for the design and use of animated algorithms in teaching computer algorithms and

  7. The use of animal infection models to study the pathogenesis of melioidosis and glanders.

    Science.gov (United States)

    Woods, Donald E

    2002-11-01

    The use of animal infection models is central to the study of microbial pathogenesis. In combination with genetic, immunological and antigen purification techniques, much can be learned regarding the pathogenesis of diseases caused by microorganisms. This update focuses on the recent use of animal infection models to study the pathogenesis of melioidosis and glanders.

  8. Contribution of animal studies to evaluate the similarity of biosimilars to reference products

    NARCIS (Netherlands)

    van Meer, Peter; Ebbers, Hans C; Kooijman, Marlous; Wied, Christine C Gispen-de; Silva-Lima, Beatriz; Moors, Ellen H M; Schellekens, Huub

    2015-01-01

    The European Union (EU) was the first region to establish a regulatory framework for biosimilars, in which animal studies are required to confirm similarity to a reference product. However, animal studies described in European public assessment reports (EPARs) or marketing authorisation applications

  9. The Scientific Value of Non-Clinical Animal Studies in Drug Development

    NARCIS (Netherlands)

    van Meer, P.J.K.

    2013-01-01

    Animal studies are considered needed as predictive models to evaluate safety and efficacy of new pharmaceuticals and are required by law. However, the scientific basis of the current paradigm on the predictability of animal studies for the effects of drugs in man is under discussion. Therefore, in

  10. The Scientific Value of Non-Clinical Animal Studies in Drug Development

    NARCIS (Netherlands)

    van Meer, P.J.K.

    2013-01-01

    Animal studies are considered needed as predictive models to evaluate safety and efficacy of new pharmaceuticals and are required by law. However, the scientific basis of the current paradigm on the predictability of animal studies for the effects of drugs in man is under discussion. Therefore, in t

  11. Toxicokinetic assessment of methylphenidate (Ritalin) in a 13-week oral toxicity study in dogs.

    Science.gov (United States)

    Bakhtiar, Ray; Ramos, Luis; Tse, Francis L S

    2004-01-01

    Ritalin or methylphenidate (MPH) is often prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. The therapeutic activity of MPH is principally due to D-threo-[2R,2'R]-MPH. Hence, in order to establish a kinetic relationship between doses and exposure levels in a non-rodent species, a 13-week oral (capsule) toxicity study of D-threo-[2R,2'R]-MPH was performed in beagle dogs. A previously reported chiral liquid chromatography tandem mass spectrometry (LC-MS/MS) with a limit of quantification (LLOQ) of 1.09 ng/ml was utilized. The results of this study indicated that MPH appeared to be rapidly absorbed in dogs following oral administration. The peak concentration was reached within 1-2 h. Based on the area under the curve (AUC) values, the plasma exposure of D-MPH was over-proportional to the dose. With the exception of two groups of animals (male/female, 7.5 mg/kg/day on day 1 and male/female, 3.0 mg/kg/day on week 7), the data showed no difference in MPH concentrations between the male and female dogs. Taking the statistical variations into account, concentrations of D-MPH that were observed after 7.5 mg/kg/day doses of D-MPH and 15 mg/kg/day doses of the racemate were similar. Following the racemate doses, the concentrations of L-MPH were consistently higher than those of the D-isomer. No accumulation of MPH was observed after 13 weeks of repeated daily administration.

  12. Methods of acute biological assays in guinea-pigs for the study of toxicity and innocuity of drugs and chemicals

    Directory of Open Access Journals (Sweden)

    Gui Mi Ko

    2010-06-01

    Full Text Available In this study, 602 samples were tested by the following assays performed at the animal facilities (Cedeme of the Federal University of São Paulo (UNIFESP: 385 for dermal irritability, 90 for ocular irritability (discontinued in 1995, 31 for systemic toxicity by injection, 26 for oral acute toxicity, 15 for toxicity by intracutaneous injection, 15 for skin sensitization, 15 for toxicity of serum and vaccines for human use, 14 for toxicity by intramuscular implantation, 7 for pyrogens, 2 for acute dermal toxicity, and 2 for irritation of mucous membrane. The following agents were tested: cosmetics and related substances (42.0%, chemicals used in industry (32.9%, plastics, rubber, and other polymers (15.9%, agrotoxics (4.0%, medicines (2.7%, and vaccines (2.5%. In the present description, emphasis was given to tests of dermal irritability and sensitization. This work was conducted entirely in animal facilities, according to our general belief that animal facilities at universities, while considering ethic principles and sanitary, genetic, nutritional, and pathophysiological controls, also require laboratories specialized in areas such as transgenics, cryopreservation, ambiental physiology, functional genomics, alternative models, and mainly activities and research on methods in toxicology, as focused in this study.Descrevemos os testes usados em ensaios biológicos de curta duração para estudo de toxicidade e inocuidade de cosméticos, fármacos e outras substâncias químicas, feitos no Biotério Central/Cedeme da Unifesp, de 1986 a 2000. Testamos 602 amostras nos seguintes ensaios: 385 de irritação cutânea, 90 de irritação ocular (até 1995, 31 de toxicidade sistêmica por injeção, 26 de toxicidade oral aguda, 15 de toxicidade por aplicação intracutânea, 15 de sensibilização da pele, 15 de toxicidade de soros e vacinas de uso humano, 14 de toxicidade por implantação intramuscular, 7 de pirogênio, 2 de toxicidade dérmica aguda e

  13. A study on African animal trypanosomosis in four areas of Senegal

    OpenAIRE

    Ravel, Sophie; Mediannikov, Oleg; Bossard, G.; Desquesnes, M; Cuny, Gérard; Davoust, B.

    2015-01-01

    In Senegal, several areas provide great potential for agriculture and animal production, but African animal trypanosomosis (AAT) is one of the major constraints to the development of more effective livestock production systems. A study was conducted to assess the current situation of AAT in this country. Surveys were carried out between June 2011 and September 2012 in four different areas: Dakar, Sine Saloum, Kedougou region and Basse Casamance in several animal species: dogs (152), donkeys (...

  14. Isoniazid Toxicity among an Older Veteran Population: A Retrospective Cohort Study.

    Science.gov (United States)

    Vinnard, Christopher; Gopal, Anand; Linkin, Darren R; Maslow, Joel

    2013-01-01

    our objective was to determine the incidence of toxicity among veterans initiating isoniazid therapy for latent tuberculosis infection (LTBI) and determine whether advancing age was a risk factor for toxicity. we performed a retrospective cohort study among all adults initiating isoniazid treatment for LTBI at a Veterans Medical Center from 1999 to 2005. We collected data on patient demographics, co-morbidities, site of initiation, and treatment outcome. 219 patients initiated isoniazid therapy for LTBI during the period of observation, and the completion of therapy was confirmed in 100 patients (46%). Among 18/219 patients (8%) that discontinued therapy due to a documented suspected toxicity, the median time to onset was 3 months (IQR 1-5 months). In an adjusted Cox regression model, there was no association between discontinuation due to suspected toxicity and advancing age (HR 1.03, 95% CI 0.99, 1.07). In contrast, hepatitis C infection was a significant predictor of cessation due to toxicity in the adjusted analysis (HR 3.03, 95% CI 1.08, 8.52). cessation of isoniazid therapy due to suspected toxicity was infrequently observed among a veteran population and was not associated with advancing age. Alternative LTBI treatment approaches should be further examined in the veteran population.

  15. Isoniazid Toxicity among an Older Veteran Population: A Retrospective Cohort Study

    Directory of Open Access Journals (Sweden)

    Christopher Vinnard

    2013-01-01

    Full Text Available Background: our objective was to determine the incidence of toxicity among veterans initiating isoniazid therapy for latent tuberculosis infection (LTBI and determine whether advancing age was a risk factor for toxicity. Methods: we performed a retrospective cohort study among all adults initiating isoniazid treatment for LTBI at a Veterans Medical Center from 1999 to 2005. We collected data on patient demographics, co-morbidities, site of initiation, and treatment outcome. Results: 219 patients initiated isoniazid therapy for LTBI during the period of observation, and the completion of therapy was confirmed in 100 patients (46%. Among 18/219 patients (8% that discontinued therapy due to a documented suspected toxicity, the median time to onset was 3 months (IQR 1–5 months. In an adjusted Cox regression model, there was no association between discontinuation due to suspected toxicity and advancing age (HR 1.03, 95% CI 0.99, 1.07. In contrast, hepatitis C infection was a significant predictor of cessation due to toxicity in the adjusted analysis (HR 3.03, 95% CI 1.08, 8.52. Conclusions: cessation of isoniazid therapy due to suspected toxicity was infrequently observed among a veteran population and was not associated with advancing age. Alternative LTBI treatment approaches should be further examined in the veteran population.

  16. Comparative QSAR studies on toxicity of phenol derivatives using quantum topological molecular similarity indices.

    Science.gov (United States)

    Hemmateenejad, Bahram; Mehdipour, Ahmad R; Miri, Ramin; Shamsipur, Mojtaba

    2010-05-01

    Quantitative structure activity relationship (QSAR) analyses using a novel type of electronic descriptors called quantum topological molecular similarity (QTMS) indices were operated to describe and compare the mechanisms of toxicity of phenols toward five different strains (i.e., Tetrahymena pyriformis, L1210 Leukemia, Pseudomonas putida, Raja japonica and Cucumis sativus). The appropriate QSAR models for the toxicity data were obtained separately employing partial least squares (PLS) regression combined with genetic algorithms (GA), as a variable selection method. The resulting QSAR models were used to identify molecular fragments of phenol derivatives whose electronic properties contribute significantly to the observed toxicities. Using this information, it was feasible to discriminate between the mechanisms of action of phenol toxicity to the studied strains. It was found that toxicities of phenols to all strains, except with L1210 Leukemia, are significantly affected by electronic features of the phenolic hydroxyl group (C-O-H). Meanwhile, the resulting models can describe the inductive and resonance effects of substituents on various toxicities.

  17. Correlation Study of Toxicity of Substituted Phenols to River Bacteria and Their Biodegradability in River Water

    Institute of Scientific and Technical Information of China (English)

    XING YUAN; GUAN-GHUA LU; LI-MIN SU

    2005-01-01

    Objective To study the correlation of toxicity with biodegradability (BODT) in order to promote QSBR development and understand the degradation mechanism. Methods Toxicity of substituted phenols to river bacteria was determined by the turbidities that were measured using a spectrophotometer (UV-190) at 530 nm against a blank control. The biodegradability of substituted phenols was expressed as BODT and the DO concentrations were determined by the iodometric titration method. Results The BODT and toxicity(log 1/IC50) of 12 substituted phenols to bacteria from the Songhua River were determined respectively. The correlation of biodegradability with toxicity was developed: BODT=8.21 (±2.22) pKa -32.44 (±8.28) log 1/IC50 +89.04 (±38.20), n=12, R2=0.791, R2(adj)=0.745, SE=9.134, F=17.066, P=0.001. Conclusion The BODT of substituted phenols was influenced by their toxicity and the ionization constant pKa. The stronger the toxicity, the less readily the compound was degraded by river bacteria.

  18. Study on the developmental toxicity of combined artesunate and mefloquine antimalarial drugs on rats.

    Science.gov (United States)

    Boareto, Ana Cláudia; Müller, Juliane Centeno; de Araujo, Samanta Luiza; Lourenço, Ana Carolina; Lourenço, Emerson Luiz Botelho; Gomes, Caroline; Minatovicz, Bruna; Lombardi, Natália; Paumgartten, Francisco Roma; Dalsenter, Paulo Roberto

    2012-12-01

    Antimalarial drug combinations containing artemisinins (ACTs) have become first choice therapies for Plasmodium falciparum malaria. Data on safety of ACTs in pregnancy are limited and no previous study has been conducted on the developmental toxicity of artesunate-mefloquine combinations on the first trimester of gestation. To evaluate the developmental toxicity of an artesunate/mefloquine combination, pregnant rats were treated orally with artesunate (15 and 40 mg/kg bwt/day), mefloquine (30 and 80 mg/kg bwt/day) and artesunate/mefloquine (15/30 and 40/80 mg/kg bwt/day) on gestation days 9-11. Dams were C-sectioned on day 20, and their uteri and fetuses removed and examined for soft tissue and skeleton abnormalities. Artesunate increased embryolethality and the incidence of limb long bone malformations on the absence of overt maternal toxicity. Mefloquine (80 mg/kg bwt/day) was maternally toxic and enhanced fetal variations. Combination of artesunate and mefloquine did not enhance their toxicity compared to the toxicity observed after its separate administration. Embryotoxicity of artesunate was apparently attenuated when it is co-administered with mefloquine.

  19. Cytotoxicity and Oral Acute Toxicity Studies of Lantana camara Leaf Extract

    Directory of Open Access Journals (Sweden)

    Badakhshan Mahdi Pour

    2011-05-01

    Full Text Available Background: The objective of this study was to investigate the toxicity of Lantana camara methanol extract. Methods: In order to evaluate the toxicity of Lantana camara, the acute toxicity of the methanolic extract on adult mice and cytotoxicity test on Vero cell line were investigated. A fixed large dose of 2 g/kg body weight of L. camara leaf extract was administrated by a single oral gavage according to the OECD procedure. Results: In 2 weeks, L. camara leaf extract showed no obvious acute toxicity. While female mice lost body weight after being treated with single dose of leaf extract in acute toxicity test, male ones lost organ mass, particularly for heart and kidney. The biochemical liver function tests showed significantly elevated TBIL and ALT in the L. camara leaf extract treated female mice group compared with the control group. Cytotoxicity effect of leaf extract of L. camara was estimated through a MTT assay. Cytotoxicity tests on Vero cell line disclosed that leaf extract at concentrations up to 500 µg/mL inhibited the growth of cells 2.5 times less than did Triton 100× 1%. More interestingly, the cytotoxicity initiated to decline at elevated concentrations of this extract. Conclusions: The results of both tests confirm that L. camara shows a pro toxic effect.

  20. The usefulness of systematic reviews of animal experiments for the design of preclinical and clinical studies.

    Science.gov (United States)

    de Vries, Rob B M; Wever, Kimberley E; Avey, Marc T; Stephens, Martin L; Sena, Emily S; Leenaars, Marlies

    2014-01-01

    The question of how animal studies should be designed, conducted, and analyzed remains underexposed in societal debates on animal experimentation. This is not only a scientific but also a moral question. After all, if animal experiments are not appropriately designed, conducted, and analyzed, the results produced are unlikely to be reliable and the animals have in effect been wasted. In this article, we focus on one particular method to address this moral question, namely systematic reviews of previously performed animal experiments. We discuss how the design, conduct, and analysis of future (animal and human) experiments may be optimized through such systematic reviews. In particular, we illustrate how these reviews can help improve the methodological quality of animal experiments, make the choice of an animal model and the translation of animal data to the clinic more evidence-based, and implement the 3Rs. Moreover, we discuss which measures are being taken and which need to be taken in the future to ensure that systematic reviews will actually contribute to optimizing experimental design and thereby to meeting a necessary condition for making the use of animals in these experiments justified.

  1. The Usefulness of Systematic Reviews of Animal Experiments for the Design of Preclinical and Clinical Studies

    Science.gov (United States)

    de Vries, Rob B. M.; Wever, Kimberley E.; Avey, Marc T.; Stephens, Martin L.; Sena, Emily S.; Leenaars, Marlies

    2014-01-01

    The question of how animal studies should be designed, conducted, and analyzed remains underexposed in societal debates on animal experimentation. This is not only a scientific but also a moral question. After all, if animal experiments are not appropriately designed, conducted, and analyzed, the results produced are unlikely to be reliable and the animals have in effect been wasted. In this article, we focus on one particular method to address this moral question, namely systematic reviews of previously performed animal experiments. We discuss how the design, conduct, and analysis of future (animal and human) experiments may be optimized through such systematic reviews. In particular, we illustrate how these reviews can help improve the methodological quality of animal experiments, make the choice of an animal model and the translation of animal data to the clinic more evidence-based, and implement the 3Rs. Moreover, we discuss which measures are being taken and which need to be taken in the future to ensure that systematic reviews will actually contribute to optimizing experimental design and thereby to meeting a necessary condition for making the use of animals in these experiments justified. PMID:25541545

  2. Laboratory studies of imitation/field studies of tradition: towards a synthesis in animal social learning.

    Science.gov (United States)

    Galef, Bennett G

    2015-03-01

    Here I discuss: (1) historical precedents that have resulted in comparative psychologists accepting the two-action method as the "gold standard" in laboratory investigations of imitation learning, (2) evidence suggesting that the two-action procedure may not be adequate to answer questions concerning the role of imitation in the development of traditional behaviors of animals living in natural habitat, and (3) an alternative approach to the laboratory study of imitation that might increase the relevance of laboratory studies of imitation to the work of behavioral ecologists/primatologists interested in animal traditions and their relationship to human cumulative culture. This article is part of a Special Issue entitled: Tribute to Tom Zentall.

  3. Determinants associated with veterinary antimicrobial prescribing in farm animals in the Netherlands: a qualitative study.

    Science.gov (United States)

    Speksnijder, D C; Jaarsma, A D C; van der Gugten, A C; Verheij, T J M; Wagenaar, J A

    2015-04-01

    Antimicrobial use in farm animals might contribute to the development of antimicrobial resistance in humans and animals, and there is an urgent need to reduce antimicrobial use in farm animals. Veterinarians are typically responsible for prescribing and overseeing antimicrobial use in animals. A thorough understanding of veterinarians' current prescribing practices and their reasons to prescribe antimicrobials might offer leads for interventions to reduce antimicrobial use in farm animals. This paper presents the results of a qualitative study of factors that influence prescribing behaviour of farm animal veterinarians. Semi-structured interviews with eleven farm animal veterinarians were conducted, which were taped, transcribed and iteratively analysed. This preliminary analysis was further discussed and refined in an expert meeting. A final conceptual model was derived from the analysis and sent to all the respondents for validation. Many conflicting interests are identifiable when it comes to antimicrobial prescribing by farm animal veterinarians. Belief in the professional obligation to alleviate animal suffering, financial dependency on clients, risk avoidance, shortcomings in advisory skills, financial barriers for structural veterinary herd health advisory services, lack of farmers' compliance to veterinary recommendations, public health interests, personal beliefs regarding the veterinary contribution to antimicrobial resistance and major economic powers are all influential determinants in antimicrobial prescribing behaviour of farm animal veterinarians. Interventions to change prescribing behaviour of farm animal veterinarians could address attitudes and advisory skills of veterinarians, as well as provide tools to deal with (perceived) pressure from farmers and advisors to prescribe antimicrobials. Additional (policy) measures could probably support farm animal veterinarians in acting as a more independent animal health consultant.

  4. A Study on the Single-dose Oral Toxicity of Super Key in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Jinhee Kim

    2015-09-01

    Full Text Available Objectives: This study was performed to analyze the single-dose oral toxicity of the super key (processed sulfur. Methods: All experiments were conducted at Medvill, an institution authorized to perform non-clinical studies, under the Good Laboratory Practice (GLP regulations. In order to investigate the oral toxicity of super key We administered it orally to Sprague-Dawley (SD rats. The SD rats were divided into four groups of five male and five female animals per group: group 1 being the control group and groups 2, 3, and 4 being the experimental groups. Doses of super key 500 mg/kg, 1,000 mg/kg and 2,000 mg/kg were administered to the experimental groups, and a dose of normal saline solution, 10 mL/kg, was administered to the control group. We examined the survival rates, weights, clinical signs, gross findings and necropsy findings. This study was conducted under the approval of the Institutional Animal Ethics Committee. (Approval number: A01-14018. Results: No deaths or abnormalities occurred in any of the four groups. Although slight decreases in the weights of some female rats were noted, no significant changes in weights or differences in the gross findings between the control group and the experimental groups were observed. To check for abnormalities in organs, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs. Conclusion: The results of this research showed that administration of 500 ─ 2,000 mg/kg of super key did not cause any changes in the weights or in the results of necropsy examinations. Neither did it result in any mortalities. The above findings suggest that treatment with super key is relatively safe. Further studies on this subject are needed to yield more concrete evidence.

  5. Safety assessment of methanol extract of red dragon fruit (Hylocereus polyrhizus): acute and subchronic toxicity studies.

    Science.gov (United States)

    Hor, Sook Yee; Ahmad, Mariam; Farsi, Elham; Yam, Mun Fei; Hashim, Mohd Akmal; Lim, Chung Pin; Sadikun, Amirin; Asmawi, Mohd Zaini

    2012-06-01

    Recently, the fruits of Hylocereus polyrhizus, known as red dragon fruit, have received much attention from growers worldwide. However, there is little toxicological information regarding the safety of repeated exposure to these fruits. The present study evaluated the potential toxicity of a methanol extract of H. polyrhizus fruit after acute and subchronic administration in rats. In the acute toxicity study, single doses of fruit extract (1250, 2500 and 5000 mg/kg) were administered to rats by oral gavage, and the rats were then monitored for 14 days. In the subchronic toxicity study, the fruit extract was administered orally to rats at doses of 1250, 2500 and 5000 mg/kg/day for 28 days. There was no mortality or signs of acute or subchronic toxicity. There was no significant difference in body weight, relative organ weight or hematological parameters in the subchronic toxicity study. Biochemical analysis showed some significant changes, including creatinine, globulin, total protein and urea levels. No abnormality of internal organs was observed between treatment and control groups. The lethal oral dose of the fruit extract is more than 5000 mg/kg and the no-observed-adverse-effect level (NOAEL) of the extract for both male and female rats is considered to be 5000 mg/kg per day for 28 days. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Toxicity and carcinogenicity studies of Ginkgo biloba extract in rat and mouse: liver, thyroid, and nose are targets.

    Science.gov (United States)

    Rider, Cynthia V; Nyska, Abraham; Cora, Michelle C; Kissling, Grace E; Smith, Cynthia; Travlos, Gregory S; Hejtmancik, Milton R; Fomby, Laurene M; Colleton, Curtis A; Ryan, Michael J; Kooistra, Linda; Morrison, James P; Chan, Po C

    2014-07-01

    Ginkgo biloba extract (GBE) is a popular herbal supplement that is used to improve circulation and brain function. In spite of widespread human exposure to relatively high doses over potentially long periods of time, there is a paucity of data from animal studies regarding the toxicity and carcinogenicity associated with GBE. In order to fill this knowledge gap, 3-month and 2-year toxicity and carcinogenicity studies with GBE administered by oral gavage to B6C3F1/N mice and F344/N rats were performed as part of the National Toxicology Program's Dietary Supplements and Herbal Medicines Initiative. The targets of GBE treatment were the liver, thyroid, and nose. These targets were consistent across exposure period, sex, and species, albeit with varying degrees of effect observed among studies. Key findings included a notably high incidence of hepatoblastomas in male and female mice and evidence of carcinogenic potential in the thyroid gland of both mice and rats. Various nonneoplastic lesions were observed beyond control levels in the liver, thyroid gland, and nose of rats and mice administered GBE. Although these results cannot be directly extrapolated to humans, the findings fill an important data gap in assessing risk associated with GBE use.

  7. BIOCHEMICAL STUDIES ON HEPATO AND NEPHROPROTECTIVE EFFECT OF BUTTERFLY TREE (BAUHINIA PURPUREA LINN. AGAINST ACETAMINOPHEN INDUCED TOXICITY

    Directory of Open Access Journals (Sweden)

    T. Sivanagi Reddy

    2012-06-01

    Full Text Available The present study was carried out to evaluate the hepato and nephroprotective activity of ethanolic extract of stem bark of Bauhinia purpurea against paracetamol induced toxicity in rats. 100, 200 and 400 mg/kg, Oral doses of ethanolic extract of stem bark of Bauhinia purpurea was administered to group of animals for 14 days. Silymarin (25 mg/kg served as a standard and paracetamol suspension at a dose of 750 mg/kg, Body weight, was used to induce liver and kidney damage. Parameters of study were glutamate oxaloacetate transaminase (GOT, glutamate pyruvate transaminase (GPT, alkaline phosphatase (ALP, bilirubin, triglycerides and total protein as liver function tests, blood urea nitrogen (BUN, creatinine and urea as kidney function tests. Biochemical studies showed increase in the levels of serum GOT, GPT, ALP, total bilirubin, triglycerides, BUN, creatinine and urea and reduction in the levels of total protein in paracetamol induced groups. These values are retrieved significantly (p< 0.05 in a dose dependant manner by treatment with ethanolic extracts of Bauhinia purpurea stem bark at three different doses. The overall result suggests that the ethanolic extract of stem bark of Bauhinia purpurea possesses hepato and nephroprotective activity against paracetamol induced toxicity.

  8. Recent advances in the management of autoimmune myocarditis: insights from animal studies.

    Science.gov (United States)

    Tajiri, Kazuko; Yasutomi, Yasuhiro; Aonuma, Kazutaka

    2016-01-01

    A growing body of evidence has been accumulating to demonstrate that human myocarditis and dilated cardiomyopathy involve a complex interaction with autoimmunity triggered by cardiotropic microbial infections. Animal experiments have provided direct evidence that infections with a particular microbe can incite autoimmune myocarditis, and this autoimmune response can be mimicked by immunization with the cardiac autoantigen, α- myosin. Animal models greatly advanced our understanding of the molecular mechanisms of myocarditis, and various novel therapeutic strategies have been reported during the last two decades. In this review we present animal models of autoimmune myocarditis and describe the outlook of possible drug targets by showing the latest findings from animal studies.

  9. A Study of Trend of Animal Experimentation in Medical Education in India

    Directory of Open Access Journals (Sweden)

    Jaswant Rai, Amandeep Singh

    2006-04-01

    Full Text Available A debate on the continuation or discontinuation of animal experiments in pharmacological practicalteaching of medical undergraduates is still in progress.The present study has been done to know thecurrent status of animal experiments in medical education in India using structured questionary. 81.25%pharmacologists and 74% of the medical graduates and clinicians favour the continuation of animalexperiments, preferably with the refinement or reduction of use of animals.Animal based experimentsplay a pivotal role in pharmacological teaching and research in India. However the pattern of practicalpharmacology teaching is not uniform and specific guidelines should be framed to ensure uniformity.

  10. A Contrastive Study of Chinese and English Animal-metaphor Idioms-A Sociolinguistic Perspective

    Institute of Scientific and Technical Information of China (English)

    ZHANG Lu-lu

    2015-01-01

    Human beings and animals have been being bound together inextricably, so it is not surprising that there is many a word and expression about animals in languages, including Chinese and English. Idiom, as one of the important and refined component parts of language, is also of such kind. This paper attempts to make a contrastive study of similarities and differences between Chi⁃nese and English animal-metaphor idioms. It also investigates into the causes for similarities and differences between Chinese and English animal-metaphor idioms from a sociolinguistic perspective.

  11. A comparative study about toxicity of CdSe quantum dots on reproductive system development of mice and controlling this toxicity by ZnS coverage

    Directory of Open Access Journals (Sweden)

    Akram Valipoor

    2015-10-01

    Full Text Available Objective(s:Medicinal benefits of quantum dots have been proved in recent years but there is little known about their toxicity especially in vivo toxicity. In order to use quantum dots in medical applications, studies ontheir in vivo toxicity is important. Materials and Methods: CdSe:ZnS quantum dots were injected in 10, 20, and 40 mg/kg doses to male mice10 days later, mice were sacrificed and five micron slides were prepared structural and optical properties of quantum dots were evaluated using XRD. Results:  Histological studies of testis tissue showed high toxic effect of CdSe:ZnS  in 40 mg/kg group. Histological studies of epididymis did not show any effect of quantum dots in terms of morphology and tube structure. Mean concentration of LH and testosterone and testis weight showed considerable changes in mice injected with 40 mg/kg dose of CdSe:ZnS compared to control group. However, FSH and body weight did not show any difference with control group. Conclusion: Although it has been reported that CdSe is highly protected from the environment by its shell, but  this study showed high toxicity for CdSe:ZnS when it is used in vivo which could be suggested that shell could contribute to increased toxicity of quantum dots. Considering lack of any previous study on this subject, our study could potentially be used as an basis for further extensive studies investigating the effects of quantum dots toxicity on development of male sexual system.

  12. Chronic toxicity and carcinogenicity study of isomalt in rats and mice.

    Science.gov (United States)

    Smits-Van Prooije, A E; De Groot, A P; Dreef-Van der Meulen, H C; Sinkeldam, E J

    1990-04-01

    The chronic toxicity and possible carcinogenicity of the sugar replacer isomalt was studied in Wistar rats and Swiss mice. Groups of 50 animals of each sex were fed 0, 2.5, 5 or 10% isomalt in the diet for nearly 2.5 yr (rats) or 2 yr (mice). Control groups received either basal diet with 10% maize starch or basal diet with 10% sucrose. Additional groups of ten rats/sex were fed the same diets and were killed after 1 yr. Isomalt and sucrose were included in the diet at the expense of maize starch. Administration of isomalt was started, in rats, in utero, and in mice, at weaning age. Feeding isomalt did not affect the appearance or behaviour of rats or mice, nor did it cause diarrhoea. Mortality rate was unaffected. Body weights of rats and mice fed 10% isomalt were generally slightly lower than those of controls. Periodic examinations of rats for haematological criteria, clinical chemistry of the blood, urine composition and kidney function did not reveal any changes of toxicological significance. Periodic haematological examinations of mice were likewise negative. Caecal enlargement was observed in rats and mice of the high-dose group, but the microscopic structure of the caecal wall was unaffected. An increased number of treated male and female rats showed hyperplasia of the urothelium in the renal pelvis accompanied by mineralization, whereas the number of females showing corticomedullary mineralization was decreased in the treated groups. The incidence, type or location of neoplasia provided no evidence of a carcinogenic potential of isomalt. Feeding 10% sucrose did not induce significant differences compared with the controls fed 10% maize starch, whereas isomalt at levels of up to 10% produced some of the changes that are common to rats fed high levels of poorly digestible carbohydrates.

  13. Histological Studies of Atrazine Toxicity on the Thyroid Gland in Rats

    Institute of Scientific and Technical Information of China (English)

    I.N.KORNILOVSKAYA; M.V.GORELAYA; 等

    1996-01-01

    Little is known about the toxic activity of the atrazine(a herbicide,commonly used in agricultural production)on the thyroid gland.In this study the compound was administered orally in female albino rats at subletal exposure equivalent to 0.2 LD50 doses for 6 and 12 days.At termination of dosing the anesthetized animals were killed and blood was drawn fo the determination of serum triiodothyronine(T3)and thyroxin(T4).A dose-dependent decrease of serum T3 concentration was observed in all the groups (control:0.5nmol·L-1,6days:0.35nmol·L-1,12days:0.21nmol·L-1).The thyroid gland was examined light-microscopically.Bouin's solution-fixed thyroids were embedded in paraffin and sections cut at 6μm ,stained separately with toluidine blue according to Slinchenko's method.Histologically in experimental groups epithelium featured small cuboidal cells and occasional structures of the follicles confluence within epitheliomers.A dose-dependent changes of the following parameters were observed:(a)increasing of number of follicle-building thyroid cells;(b) increasing of tollicular volume;(c) decreasing of nucleus volume.Investigation of the whole population of thyroid mast cells disclosed no change in degranulation intensity.By contrast,Degranulation intensity was decreased in perifollicular mast cells from groups treated with atrazine in dose-dependent manner.There are no changes observed in degranulation of stromal mast cells.These results suggesting that differences in response to the atrazine might account for an aspect of the functional heterogeneit within the rat thyroid mast cell population.

  14. A step-by-step guide to systematically identify all relevant animal studies.

    Science.gov (United States)

    Leenaars, Marlies; Hooijmans, Carlijn R; van Veggel, Nieky; ter Riet, Gerben; Leeflang, Mariska; Hooft, Lotty; van der Wilt, Gert Jan; Tillema, Alice; Ritskes-Hoitinga, Merel

    2012-01-01

    Before starting a new animal experiment, thorough analysis of previously performed experiments is essential from a scientific as well as from an ethical point of view. The method that is most suitable to carry out such a thorough analysis of the literature is a systematic review (SR). An essential first step in an SR is to search and find all potentially relevant studies. It is important to include all available evidence in an SR to minimize bias and reduce hampered interpretation of experimental outcomes. Despite the recent development of search filters to find animal studies in PubMed and EMBASE, searching for all available animal studies remains a challenge. Available guidelines from the clinical field cannot be copied directly to the situation within animal research, and although there are plenty of books and courses on searching the literature, there is no compact guide available to search and find relevant animal studies. Therefore, in order to facilitate a structured, thorough and transparent search for animal studies (in both preclinical and fundamental science), an easy-to-use, step-by-step guide was prepared and optimized using feedback from scientists in the field of animal experimentation. The step-by-step guide will assist scientists in performing a comprehensive literature search and, consequently, improve the scientific quality of the resulting review and prevent unnecessary animal use in the future.

  15. Toxicological studies for some agricultural waste extracts on mosquito larvae and experimental animals

    Institute of Scientific and Technical Information of China (English)

    Somia El-Maghraby; Galal A Nawwar; Reda FA Bakr; Nadia Helmy; Omnia MHM Kamel

    2012-01-01

    Objective: To evaluate some agricultural waste extracts as insecticide and their effects on enzyme activities in liver and kidney of male mice. Methods: The insecticidal activity of five tested compounds (one crude extract and 4 waste compounds) was bioassay against the 3rd instars of the Culex pipiens (Cx. pipiens) larvae in the laboratory. The LC50 values of eucalyptol, apricot kernel, Rice bran, corn, black liquor and white liquor are 91.45, 1 166.1, 1 203.3, 21 449.65, 4 025.78 and 6 343.18 ppm, respectively. Selection of the compounds for the subsequent studies was not only dependent on LC50 values but also on the persistence of these wastes products on large scale. Results:White and black liquor did not produce any gross effect at 200 mg/Kg body weight. No apparent toxic symptoms were observed in tested animals during the whole period of the experiment which run out for 14 days. No statistically significance was observed in the enzyme cholinesterase activity, the activities of liver enzymes and kidney function in treated mice with black and white liquors. While, no and slight inhibition was observed after the 2 weeks of treatment period with deltamethrin and fenitrothion reached to about 24%in plasma cholinesterase enzyme activity. Significantly increase in the activities of liver enzymes and kidney function in treated mice with deltamethrin and fenitrothion. Conclusions:Black liquor can be used efficiently to control Cx. pipiens larvae under laboratory condition. Environmental problem caused by rice straw can be solved by converting the waste material to beneficial natural selective insecticide.

  16. Modular endoprosthesis for mandibular reconstruction: a preliminary animal study.

    NARCIS (Netherlands)

    Lee, S.; Goh, B.T.; Tideman, H.; Stoelinga, P.J.W.

    2008-01-01

    The use of a mandibular modular endoprosthesis after segmental resection of part of the body of the mandible was studied. This preliminary study was carried out on four pigs and four monkeys. The devices were made of a titanium alloy and were cemented in the prepared medullary spaces with polymethyl

  17. Reducing the number of laboratory animals used in tissue engineering research by restricting the variety of animal models. Articular cartilage tissue engineering as a case study.

    Science.gov (United States)

    de Vries, Rob B M; Buma, Pieter; Leenaars, Marlies; Ritskes-Hoitinga, Merel; Gordijn, Bert

    2012-12-01

    The use of laboratory animals in tissue engineering research is an important underexposed ethical issue. Several ethical questions may be raised about this use of animals. This article focuses on the possibilities of reducing the number of animals used. Given that there is considerable debate about the adequacy of the current animal models in tissue engineering research, we investigate whether it is possible to reduce the number of laboratory animals by selecting and using only those models that have greatest predictive value for future clinical application of the tissue engineered product. The field of articular cartilage tissue engineering is used as a case study. Based on a study of the scientific literature and interviews with leading experts in the field, an overview is provided of the animal models used and the advantages and disadvantages of each model, particularly in terms of extrapolation to the human situation. Starting from this overview, it is shown that, by skipping the small models and using only one large preclinical model, it is indeed possible to restrict the number of animal models, thereby reducing the number of laboratory animals used. Moreover, it is argued that the selection of animal models should become more evidence based and that researchers should seize more opportunities to choose or create characteristics in the animal models that increase their predictive value.

  18. Acute and subchronic toxicity study of Tamra bhasma (incinerated copper prepared from Ashodhita (unpurified and Shodhita (purified tamra in rats

    Directory of Open Access Journals (Sweden)

    C Y Jagtap

    2013-01-01

    Full Text Available The use of metals in traditional medicines is very often seen as matter of concern these days, especially the Bhasma preparations which are always under stringent observations for containing highly reactive inorganic elements such as lead, mercury, arsenic and others. One of the Bhasma extensively used in routine Ayurvedic practice is Tamra (copper bhasma. If it is not prepared properly or Shodhana procedure is not done properly, it acts as a poison. To indicate its toxic potential, Ashtamahadoshas (eight major ill effects have been quoted in classics and due emphasis have been given to its Shodhana procedure. In the present study, Tamra bhasma prepared from Shodhita and Ashodhita Tamra was subjected to oral toxicity study to ascertain the role of Shodhana process on safety profile of Tamra bhasma on subchronic administration to albino rats. Both the samples were administered to rats for 45 consecutive days at the doses of 5.5, 27.5, and 55 mg/kg. Animals were sacrificed on 46 th day and parameters like hematological, serum biochemical, and histopathology of various organs were studied. Results showed that Tamra bhasma prepared from Ashodhita Tamra has pathological implications on different hematological, serum biochemical and cytoarchitecture of different organs even at therapeutic dose level (5.5 mg/kg. Whereas, Tamra bhasma prepared from Shodhita Tamra is safe even at five-fold to therapeutic equivalent doses (27.5 mg/kg. These observations emphasize the role of Shodhana and importance of dose in expression of toxicity of the medicinal preparations.

  19. Modulation of protein fermentation does not affect fecal water toxicity: a randomized cross-over study in healthy subjects.

    Directory of Open Access Journals (Sweden)

    Karen Windey

    Full Text Available OBJECTIVE: Protein fermentation results in production of metabolites such as ammonia, amines and indolic, phenolic and sulfur-containing compounds. In vitro studies suggest that these metabolites might be toxic. However, human and animal studies do not consistently support these findings. We modified protein fermentation in healthy subjects to assess the effects on colonic metabolism and parameters of gut health, and to identify metabolites associated with toxicity. DESIGN: After a 2-week run-in period with normal protein intake (NP, 20 healthy subjects followed an isocaloric high protein (HP and low protein (LP diet for 2 weeks in a cross-over design. Protein fermentation was estimated from urinary p-cresol excretion. Fecal metabolite profiles were analyzed using GC-MS and compared using cluster analysis. DGGE was used to analyze microbiota composition. Fecal water genotoxicity and cytotoxicity were determined using the Comet assay and the WST-1-assay, respectively, and were related to the metabolite profiles. RESULTS: Dietary protein intake was significantly higher during the HP diet compared to the NP and LP diet. Urinary p-cresol excretion correlated positively with protein intake. Fecal water cytotoxicity correlated negatively with protein fermentation, while fecal water genotoxicity was not correlated with protein fermentation. Heptanal, 3-methyl-2-butanone, dimethyl disulfide and 2-propenyl ester of acetic acid are associated with genotoxicity and indole, 1-octanol, heptanal, 2,4-dithiapentane, allyl-isothiocyanate, 1-methyl-4-(1-methylethenyl-benzene, propionic acid, octanoic acid, nonanoic acid and decanoic acid with cytotoxicity. CONCLUSION: This study does not support a role of protein fermentation in gut toxicity. The identified metabolites can provide new insight into colonic health. TRIAL REGISTRATION: ClinicalTrial.gov NCT01280513.

  20. Regulating Animal Health, Gender and Quality Control: A Study of Veterinary Surgeons in Great Britain

    Science.gov (United States)

    Enticott, Gareth

    2012-01-01

    This paper explores the validity of performance management regimes for quality assuring animal health regulation by comparing the results of tests for bovine tuberculosis (bTB) between male and female vets. In doing so it hopes to present some practical solutions to the regulation of animal disease and encourage further sociological study of the…

  1. Regulating Animal Health, Gender and Quality Control: A Study of Veterinary Surgeons in Great Britain

    Science.gov (United States)

    Enticott, Gareth

    2012-01-01

    This paper explores the validity of performance management regimes for quality assuring animal health regulation by comparing the results of tests for bovine tuberculosis (bTB) between male and female vets. In doing so it hopes to present some practical solutions to the regulation of animal disease and encourage further sociological study of the…

  2. Inter-laboratory comparison study for pyrrolizidine alkaloids in animal feed using spiked and incurred material

    NARCIS (Netherlands)

    Nijs, de W.C.M.; Elbers, I.J.W.; Mulder, P.P.J.

    2014-01-01

    Pyrrolizidine alkaloids (PAs) are hepatotoxic metabolites produced by plants. PAs in animal feed can cause acute or chronic intoxications in animals and can be transferred to milk. An inter-laboratory comparison study among 12 laboratories, using their own methods of analysis, was conducted for the

  3. Talking about Animals: Studies of Young Children Visiting Zoos, a Museum and a Farm.

    Science.gov (United States)

    Tunnicliffe, Susan Dale

    The purpose of this study was to identify the content and form of the conversations and recognize the variables that are acting during visits to animal exhibits, and the influence on conversational content of both different types of locations and animal exhibits and visit rationales. Conversations of children between the ages of 3 and 12 years and…

  4. An Exploratory Study of Animal-Assisted Interventions Utilized by Mental Health Professionals

    Science.gov (United States)

    O'Callaghan, Dana M.; Chandler, Cynthia K.

    2011-01-01

    This study implemented an exploratory analysis to examine how a sample of mental health professionals incorporates specific animal-assisted techniques into the therapeutic process. An extensive review of literature related to animal-assisted therapy (AAT) resulted in the identification of 18 techniques and 10 intentions for the practice of AAT in…

  5. Disorders of reproduction in epilepsy--what can we learn from animal studies?

    Science.gov (United States)

    Taubøll, Erik; Røste, Line Sveberg; Svalheim, Sigrid; Gjerstad, Leif

    2008-03-01

    Several animal studies have shown that both the epilepsy itself and many antiepileptic drugs (AEDs) affect reproductive endocrine function in both males and females. Epileptic activity may lead to arrested ovarian cyclicity, anovulatory cycles, polycystic ovaries, and endocrine changes in female animals. In males, seizures disturb normal reproductive physiology by inducing endocrine changes, alterations in gonadal size, and hyposexuality. Several AEDs also affect endocrine function, fertility, and gonadal morphology in both sexes. This paper reviews the literature regarding animal studies related to reproductive disorders in epilepsy. Although care should always be taken when applying data from animal experiments to the human situation, animal models provide a unique possibility for investigating the independent effects of the epilepsy itself and the effects of AEDs in isolation, without confounding factors. By constantly comparing results from clinical and animal studies, and by developing appropriate animal models, several mechanistic questions regarding the complex interplay between epilepsy, hormones, and AEDs can be explored. Animal experiments should play an integral part in the study of reproductive endocrine disorders in epilepsy.

  6. Pre-attentive processing and schizophrenia: animal studies.

    NARCIS (Netherlands)

    Ellenbroek, B.A.

    2004-01-01

    RATIONALE: Schizophrenia is characterized by a large variety of cognitive symptoms, among which information processing deficits have been extensively studied. So far, these aspects have been found to be remarkably stable and effective treatment is still lacking. Traditionally, information processing

  7. Amelioration of Acute Mercury Toxicity by a Novel, Non-Toxic Lipid Soluble Chelator N,N′bis-(2-mercaptoethyl)isophthalamide: Effect on Animal Survival, Health, Mercury Excretion and Organ Accumulation

    OpenAIRE

    Clarke, David; Buchanan, Roger; Gupta, Niladri; Haley, Boyd

    2012-01-01

    The toxic effects of mercury are known to be complex with specific enzyme inhibitions and subsequent oxidative stress adding to the damaging effects. There are likely other factors involved, such as the development of impaired metal ion homeostasis and depletion of thiol and selenium based metabolites such as cysteine and selenium. Much of the toxicity of mercury occurs at the intracellular level via binding of Hg2+ to thiol groups in specific proteins. Therefore, amelioration of mercury toxi...

  8. Study of Single-dose Toxicity of Guseonwangdo-go Glucose Intramuscular Injection in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Jo Su-jeong

    2014-03-01

    Full Text Available Objectives: This study was performed to analyze single-dose intramuscular toxicity of Guseonwangdo-go glucose pharmacopuncture. Methods: Eighty six-week-old Sprague-Dawley rats were divided into two large groups of forty rats; Guseonwangdo-go glucose 5% and Guseonwangdo-go glucose 20% groups. Each group was sub-divided into four smaller groups of five males and five females, with the following dosages of pharmacopuncture being administered by intramuscular (IM injection in each group: group 1 (G1, control group: 1.0 mL of normal saline solution, group 2 (G2, low-dose group: 0.1 mL, group 3 (G3, mid-dose group: 0.5 mL, and group 4 (G4, high-dose group: 1.0 mL. Results: No mortalities or clinical signs were observed in any group. Also, no significant changes in body weights or in hematological/biochemical analyses were observed between the control and the experimental groups during necropsy or histopathology. Conclusion: The above findings suggest that the lethal dose of Guseonwangdo-go glucose 5% and 20% pharmacopuncture administered via IM injection is more than 1.0 mL per animal in both male and female rats. Further studies on the repeated-dose toxicity of Guseonwangdo-go glucose should be conducted to yield more concrete data.

  9. OECD validation study to assess intra- and inter-laboratory reproducibility of the zebrafish embryo toxicity test for acute aquatic toxicity testing.

    Science.gov (United States)

    Busquet, François; Strecker, Ruben; Rawlings, Jane M; Belanger, Scott E; Braunbeck, Thomas; Carr, Gregory J; Cenijn, Peter; Fochtman, Przemyslaw; Gourmelon, Anne; Hübler, Nicole; Kleensang, André; Knöbel, Melanie; Kussatz, Carola; Legler, Juliette; Lillicrap, Adam; Martínez-Jerónimo, Fernando; Polleichtner, Christian; Rzodeczko, Helena; Salinas, Edward; Schneider, Katharina E; Scholz, Stefan; van den Brandhof, Evert-Jan; van der Ven, Leo T M; Walter-Rohde, Susanne; Weigt, Stefan; Witters, Hilda; Halder, Marlies

    2014-08-01

    The OECD validation study of the zebrafish embryo acute toxicity test (ZFET) for acute aquatic toxicity testing evaluated the ZFET reproducibility by testing 20 chemicals at 5 different concentrations in 3 independent runs in at least 3 laboratories. Stock solutions and test concentrations were analytically confirmed for 11 chemicals. Newly fertilised zebrafish eggs (20/concentration and control) were exposed for 96h to chemicals. Four apical endpoints were recorded daily as indicators of acute lethality: coagulation of the embryo, lack of somite formation, non-detachment of the tail bud from the yolk sac and lack of heartbeat. Results (LC50 values for 48/96h exposure) show that the ZFET is a robust method with a good intra- and inter-laboratory reproducibility (CV30%) for some very toxic or volatile chemicals, and chemicals tested close to their limit of solubility. The ZFET is now available as OECD Test Guideline 236. Considering the high predictive capacity of the ZFET demonstrated by Belanger et al. (2013) in their retrospective analysis of acute fish toxicity and fish embryo acute toxicity data, the ZFET is ready to be considered for acute fish toxicity for regulatory purposes. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Biocompatibility study of two diblock copolymeric nanoparticles for biomedical applications by in vitro toxicity testing

    Energy Technology Data Exchange (ETDEWEB)

    Goñi-de-Cerio, Felipe [GAIKER Technology Centre (Spain); Mariani, Valentina [European Commission, Nanobiosciences Unit, Institute for Health and Consumer Protection, Joint Research Centre (Italy); Cohen, Dror [Dead Sea Laboratories, AHAVA (Israel); Madi, Lea [Tel-Aviv University, Department of Physiology and Pharmacology, Sackler School of Medicine (Israel); Thevenot, Julie; Oliveira, Hugo [ENSCPB, Université de Bordeaux (France); Uboldi, Chiara; Giudetti, Guido; Coradeghini, Rosella [European Commission, Nanobiosciences Unit, Institute for Health and Consumer Protection, Joint Research Centre (Italy); Garanger, Elisabeth [ENSCPB, Université de Bordeaux (France); Rossi, François [European Commission, Nanobiosciences Unit, Institute for Health and Consumer Protection, Joint Research Centre (Italy); Portugal-Cohen, Meital; Oron, Miriam [Dead Sea Laboratories, AHAVA (Israel); Korenstein, Rafi [Tel-Aviv University, Department of Physiology and Pharmacology, Sackler School of Medicine (Israel); Lecommandoux, Sébastien [ENSCPB, Université de Bordeaux (France); Ponti, Jessica [European Commission, Nanobiosciences Unit, Institute for Health and Consumer Protection, Joint Research Centre (Italy); Suárez-Merino, Blanca; Heredia, Pedro, E-mail: heredia@gaiker.es [GAIKER Technology Centre (Spain)

    2013-11-15

    Drugs used for chemotherapy normally carry out adverse, undesired effects. Nanotechnology brings about new horizons to tackle cancer disease with a different strategy. One of the most promising approaches is the use of nanocarriers to transport active drugs. These nanocarriers need to have special properties to avoid immune responses and toxicity, and it is critical to study these effects. Nanocarriers may have different nature, but polypeptide-based copolymers have attracted considerable attention for their biocompatibility, controlled and slow biodegradability as well as low toxicity. Little has been done regarding specific nanocarriers toxicity. In this study, we performed a thorough toxicological study of two different block copolymer nanoparticles (NPs); poly(trimethylene carbonate)-block–poly(l-glutamic acid) (PTMC-b–PGA) and poly(ethylene glycol)-block–poly(γ-benzyl-l-glutamate) (PEG-b–PBLG) with sizes between 113 and 131 nm. Low blood–serum–protein interaction was observed. Moreover, general toxicity assays and other endpoints (apoptosis or necrosis) showed good biocompatibility for both NPs. Reactive oxygen species increased in only two cell lines (HepG2 and TK6) in the presence of PTMC-b–PGA. Cytokine production study showed cytokine induction only in one cell line (A549). We also performed the same assays on human skin organ culture before and after UVB light treatment, with a moderate toxicity after treatment independent of NPs presence or absence. Interleukin 1 induction was also observed due to the combined effect of PEG-b–PBLG and UVB light irradiation. Future in vivo studies for biocompatibility and toxicity will provide more valuable information, but, so far, the findings presented here suggest the possibility of using these two NPs as nanocarriers for nanomedical applications, always taking into account the application procedure and the way in which they are implemented.

  11. Biocompatibility study of two diblock copolymeric nanoparticles for biomedical applications by in vitro toxicity testing

    Science.gov (United States)

    Goñi-de-Cerio, Felipe; Mariani, Valentina; Cohen, Dror; Madi, Lea; Thevenot, Julie; Oliveira, Hugo; Uboldi, Chiara; Giudetti, Guido; Coradeghini, Rosella; Garanger, Elisabeth; Rossi, François; Portugal-Cohen, Meital; Oron, Miriam; Korenstein, Rafi; Lecommandoux, Sébastien; Ponti, Jessica; Suárez-Merino, Blanca; Heredia, Pedro

    2013-11-01

    Drugs used for chemotherapy normally carry out adverse, undesired effects. Nanotechnology brings about new horizons to tackle cancer disease with a different strategy. One of the most promising approaches is the use of nanocarriers to transport active drugs. These nanocarriers need to have special properties to avoid immune responses and toxicity, and it is critical to study these effects. Nanocarriers may have different nature, but polypeptide-based copolymers have attracted considerable attention for their biocompatibility, controlled and slow biodegradability as well as low toxicity. Little has been done regarding specific nanocarriers toxicity. In this study, we performed a thorough toxicological study of two different block copolymer nanoparticles (NPs); poly(trimethylene carbonate)- block-poly( l-glutamic acid) (PTMC- b-PGA) and poly(ethylene glycol)- block-poly( γ-benzyl- l-glutamate) (PEG- b-PBLG) with sizes between 113 and 131 nm. Low blood-serum-protein interaction was observed. Moreover, general toxicity assays and other endpoints (apoptosis or necrosis) showed good biocompatibility for both NPs. Reactive oxygen species increased in only two cell lines (HepG2 and TK6) in the presence of PTMC- b-PGA. Cytokine production study showed cytokine induction only in one cell line (A549). We also performed the same assays on human skin organ culture before and after UVB light treatment, with a moderate toxicity after treatment independent of NPs presence or absence. Interleukin 1 induction was also observed due to the combined effect of PEG- b-PBLG and UVB light irradiation. Future in vivo studies for biocompatibility and toxicity will provide more valuable information, but, so far, the findings presented here suggest the possibility of using these two NPs as nanocarriers for nanomedical applications, always taking into account the application procedure and the way in which they are implemented.

  12. Estimating the predictive validity of diabetic animal models in rosiglitazone studies.

    Science.gov (United States)

    Varga, O E; Zsíros, N; Olsson, I A S

    2015-06-01

    For therapeutic studies, predictive validity of animal models - arguably the most important feature of animal models in terms of human relevance - can be calculated retrospectively by obtaining data on treatment efficacy from human and animal trials. Using rosiglitazone as a case study, we aim to determine the predictive validity of animal models of diabetes, by analysing which models perform most similarly to humans during rosiglitazone treatment in terms of changes in standard diabetes diagnosis parameters (glycosylated haemoglobin [HbA1c] and fasting glucose levels). A further objective of this paper was to explore the impact of four covariates on the predictive capacity: (i) diabetes induction method; (ii) drug administration route; (iii) sex of animals and (iv) diet during the experiments. Despite the variable consistency of animal species-based models with the human reference for glucose and HbA1c treatment effects, our results show that glucose and HbA1c treatment effects in rats agreed better with the expected values based on human data than in other species. Induction method was also found to be a substantial factor affecting animal model performance. The study concluded that regular reassessment of animal models can help to identify human relevance of each model and adapt research design for actual research goals.

  13. Study on the removal of toxic substance from river water using O3-GAC process

    Institute of Scientific and Technical Information of China (English)

    杨玉楠; 孙志荣; 王宝贞; 杨敏; 李文兰

    2004-01-01

    This paper studied on the removal of toxic substance from river water using O3-GAC process. The result of GC/MS analysis indicated that the number of organic compound species was decreased by 55. 1%. The species of toxic substance of raw water also dec reased from 16 to 5. The total removal rate of CODMn andUV254were 45% ~ 72% and 60% ~ 80% following O3-GAC treatment. It reflected that this process had a good effective on removing unsaturation organic which absorb UV and toxic organic containing nitrogen. The results of Ames test indicated that raw water had a relatively strong mutagicity on TA 98. The O3-GAC process had a good ability in removing mutagen in water. The effluent water' s mutagicity is minus. The results of the study indicated that the effluent of the O3-GAC process was meet the demand of drinking water.

  14. The scientific basis for chelation: animal studies and lead chelation.

    Science.gov (United States)

    Smith, Donald; Strupp, Barbara J

    2013-12-01

    This presentation summarizes several of the rodent and non-human studies that we have conducted to help inform the efficacy and clinical utility of succimer (meso-2,3-dimercaptosuccincinic acid) chelation treatment. We address the following questions: (1) What is the extent of body lead, and in particular brain lead reduction with chelation, and do reductions in blood lead accurately reflect reductions in brain lead? (2) Can succimer treatment alleviate the neurobehavioral impacts of lead poisoning? And (3) does succimer treatment, in the absence of lead poisoning, produce neurobehavioral deficits? Results from our studies in juvenile primates show that succimer treatment is effective at accelerating the elimination of lead from the body, but chelation was only marginally better than the complete cessation of lead exposure alone. Studies in lead-exposed adult primates treated with a single 19-day course of succimer showed that chelation did not measurably reduce brain lead levels compared to vehicle-treated controls. A follow-up study in rodents that underwent one or two 21-day courses of succimer treatment showed that chelation significantly reduced brain lead levels, and that two courses of succimer were significantly more efficacious at reducing brain lead levels than one. In both the primate and rodent studies, reductions in blood lead levels were a relatively poor predictor of reductions in brain lead levels. Our studies in rodents demonstrated that it is possible for succimer chelation therapy to alleviate certain types of lead-induced behavioral/cognitive dysfunction, suggesting that if a succimer treatment protocol that produced a substantial reduction of brain lead levels could be identified for humans, a functional benefit might be derived. Finally, we also found that succimer treatment produced lasting adverse neurobehavioral effects when administered to non-lead-exposed rodents, highlighting the potential risks of administering succimer or other metal

  15. Protocol Development and Preliminary Toxicity Study of CBRN Nanomaterials

    Science.gov (United States)

    2013-12-05

    Schlager, and S.M. Hussain. 2009. Cyrstal Structure Mediates Mode of Cell Death in TiO2. Nanotoxicity. J Nanopart Res. 11(6):1361-1374. Cao, C.J., K...Mouse Keratinocytes. J Nanopart Res. 11:15-24. Toxicology Study No. 87-XE-0EJ5-11 (FY12 Continuation) B-1 Appendix B - Figures 10 - 1 . 0 0 10 - 0 . 7 5

  16. Arterial Clamping Increases Central Renal Cryoablation Efficacy: An Animal Study

    DEFF Research Database (Denmark)

    Nonboe, Lasse Larsen; Nielsen, Tommy Kjaergaard; Høyer, Søren;

    2017-01-01

    INTRODUCTION: The minimally invasive treatment of small renal masses with cryoablation has become increasingly widespread during the past 15 years. Studies with long-term follow-up are beginning to emerge, showing good oncological control, however, tumors with a central and endophytic location seem...... to possess an increased risk of treatment failure. Such tumors are likely to be subjected to a high volume of blood giving thermal protection to the cancerous cells. Arterial clamping during freezing might reduce this effect but at the same time subject the kidney to ischemia. The aim of this study...... was to evaluate the effect of renal artery clamping during cryoablation in a porcine survival model. METHODS: Ten Danish Landrace pigs (approximately 40 kg) underwent bilateral laparoscopic cryoablation with clamping of the right renal artery during freezing. The cryoablation consisted of a standard double...

  17. Animal trial on zinc doped hydroxyapatite: A case study

    Directory of Open Access Journals (Sweden)

    Promita Bhattacharjee

    2014-03-01

    Full Text Available Calcium hydroxyapatite (HAp has widely been used as bone substitute due to its good biocompatibility and bioactivity. In the present work, hydroxyapatite was doped with zinc (Zn to improve its bioactivity. The study reports the technique to synthesize Zn-doped HAp powder using a simple, economic route and the influence of this dopant on the physical, mechanical and biological properties of the HAp. Porous blocks were prepared by sintering at 1150 °C and the sintered samples were characterized using XRD and FTIR. In vitro bioresorption behavior of the sintered blocks was assessed in simulated body fluid (SBF maintained in a dynamic state. The in vivo study was exclusively conducted to evaluate healing of surgically created defects on the tibia of adult New Zealand rabbit after implantation of HAp. Local inflammatory reaction and healing of wound, radiological investigations, histological and SEM studies, oxytetracycline labeling and mechanical push-out test were performed up to 60 days post-operatively. It was observed that Zn substituted HAp showed better osteointegration than undoped HAp. Radiology revealed progressively less contrast between implant and surrounding bone. New bone formation in Zn-doped HAp was more prompt. Mechanical push-out test showed high interfacial strength (nearly 2.5 times between host bone and doped implant.

  18. Post-Operative Benefits of Animal-Assisted Therapy in Pediatric Surgery: A Randomised Study

    OpenAIRE

    Valeria Calcaterra; Pierangelo Veggiotti; Clara Palestrini; Valentina De Giorgis; Roberto Raschetti; Massimiliano Tumminelli; Simonetta Mencherini; Francesca Papotti; Catherine Klersy; Riccardo Albertini; Selene Ostuni; Gloria Peli